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A case of primary congenital glaucoma: A diagnostic dilemma
Optometry (2007) 78, 167-175
A case of primary congenital glaucoma: A diagnostic dilemma Nadine M. Girgis, O.D.,a,b and Kelly A. Frantz, O.D.b a
Northwest Optometric Associates, Harwood Heights, Illinois, and bIllinois College of Optometry, Chicago, Illinois. KEYWORDS Congenital glaucoma; Buphthalmos; Goniotomy; Trabeculotomy; Trabeculectomy; Amblyopia; Haab’s striae
Abstract BACKGROUND: Primary congenital glaucoma generally presents with a classic clinical triad of photophobia, blepharospasm, and epiphora caused by the corneal changes that occur secondary to increased intraocular pressure (IOP). The condition typically presents bilaterally and is rarely hereditary. Onset is from age 2 months to 2 to 3 years. CASE REPORT: A 2-year, 5-month-old Hispanic boy presented with an enlarged right eye and an intermittent right exotropia, without tearing or photophobia. Examination also found high myopia and an optic nerve cup-to-disc ratio larger in the right than the left eye. Referral to a pediatric ophthalmologist was initiated. On the first examination under anesthesia (EUA), the child was diagnosed with unilateral megalocornea with a normal IOP. He did not have any other typical signs and symptoms of primary congenital glaucoma. An EUA 8 months later led to a diagnosis of primary congenital glaucoma based on the new appearance of Haab’s striae, further enlargement of the cornea, and an elevated IOP. At this point, medical management was instituted. CONCLUSION: This case shows the importance of recognizing signs of primary congenital glaucoma so that appropriate management can begin as soon as possible to provide the best visual outcome for a child. Optometry 2007;78:167-175
Pediatric glaucoma is a broad category that includes any type of glaucoma, primary or secondary, presenting from birth to 18 years of age. The primary pediatric glaucomas are caused by congenital anomalies that affect aqueous outflow. Secondary pediatric glaucomas are caused by postbirth factors such as ocular trauma, surgery, and inflammation. The primary pediatric glaucomas are more common than the secondary glaucomas.1 Primary congenital glaucoma occurs in 1 in 10,000 children in the United States. This prevalence rate is quoted as the world average, although specific prevalence rates vary for different populations around the world from 1 in 1,250 to 1 in 22,000.2-4
Corresponding author: Nadine M. Girgis, O.D., Northwest Optometric Associates, 4970 N Harlem Avenue, Harwood Heights, Illinois 60706. E-mail: [email protected]
Seventy percent of these cases are bilateral, and 65% of the children affected are male.5 Primary pediatric glaucoma consists of many types of glaucoma, of which primary congenital glaucoma is the most prevalent. Primary congenital glaucoma consists of 3 subcategories that are categorized by age of onset, although generally in the literature the 3 types are not delineated, and are simply grouped under the term primary congenital glaucoma.1 Primary congenital glaucoma (40%) presents from birth to age 2 months. Primary infantile glaucoma (55%) presents from age 2 months to 2 or 3 years.6,7 Late-onset primary infantile glaucoma presents after 3 years of age. Juvenile-onset primary open-angle glaucoma presents anywhere from childhood into early adulthood. Primary congenital, infantile, and late-onset infantile glaucoma are caused by an isolated anomaly of the trabecular mesh-
1529-1839/07/$ -see front matter © 2007 American Optometric Association. All rights reserved. doi:10.1016/j.optm.2006.10.016
168 work (trabeculodysgenesis). For the remainder of this discussion, congenital, infantile, and late-onset infantile glaucoma all will be labeled primary congenital glaucoma because that is how they are commonly referred to in the literature. Juvenile-onset primary open-angle glaucoma is not caused by trabeculodysgenesis and presents as adult primary open-angle glaucoma. Like adult primary openangle glaucoma, the juvenile variety has an unknown pathophysiology.8,9 Primary congenital glaucoma generally presents with a classic clinical triad of photophobia, blepharospasm, and epiphora. These signs are caused by the corneal changes that occur secondary to increased intraocular pressure (IOP). Because the young eye is still distensible, high IOP can lead to enlargement of the eye, breaks in Descemet’s membrane (Haab’s striae), and stromal edema causing a cloudy cornea and optic nerve damage.1 Primary congenital glaucoma is a vision-threatening disease. Therefore, it is important to understand the signs, symptoms, and treatment for optimal management of patients. By no means is pediatric glaucoma a straightforward disease. This report presents an atypical case of congenital glaucoma with an elusive diagnosis and reviews potential differential diagnoses and treatment considerations once the disease is diagnosed.
Case A 2-year, 5-month-old Hispanic boy presented to our facility for his first eye examination. His mother brought him because she had noticed that his right eye was larger than his left eye, and his right eye intermittently turned out. Inspection of photographs supplied by the mother showed evidence of a larger right eye in pictures taken at age 8 months, but not in one taken at age 1 month (no photographs were available showing the patient at other ages). The mother denied noticing tearing or photophobia. The patient’s ocular history revealed no trauma or surgery to either eye. The patient’s medical history was unremarkable, and he used no medications. His family history was negative for glaucoma or strabismus. The patient was hesitant and uncooperative throughout the examination, although he did not appear to be experiencing any pain. He did not respond to visual acuity testing with Teller preferential looking acuity cards beyond the 20/1200 in both eyes (OU) level and did not allow occlusion of either eye. Pupils were equal, round, and reactive to light OU, without an afferent pupillary defect. Extraocular muscle motility was full for both eyes. Cover test found an intermittent right exotropia of approximately 25⌬ at distance, orthophoria at near, and no vertical component. Anterior segment evaluation found a corneal diameter of 14 mm horizontally in the right eye (O.D.) and 12 mm horizontally in the left eye (O.S.) (see Figure 1). The child showed no photophobia or tearing. Neither corneal edema
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Figure 1
Patient with right eye noticeably larger than the left at 3
years of age.
nor Haab’s striae were apparent. IOP was measured as 33, 37 mmHg O.D. and 33, 33 mmHg O.S. at 11:15 AM with a Tono-pen (Medtronic, Jacksonville, Florida) (with standard deviation [SD] less than 5% of the mean of 4 measurements). However, the patient was very agitated and uncooperative, which may have led to inaccurately higher readings.10 Postdilation retinoscopy found a ⫺5.00 diopter (D) sphere O.D., and plano O.S. The optic nerve had a cup-todisc ratio of 0.5 horizontally and vertically O.D. and 0.4 horizontally and vertically O.S. with apparently healthy rim tissue OU. A prescription was given of O.D. ⫺5.00 D sphere and O.S. plano in polycarbonate lenses for full-time wear. Based on the findings of anisometropia, unequal optic nerve appearance, the right corneal diameter larger than the left, and suspicious IOPs, referral to a pediatric ophthalmologist was instituted to rule out congenital glaucoma versus unilateral megalocornea. Two months later, the pediatric ophthalmologist performed an examination under anesthesia to obtain more accurate objective findings. IOP was 19 mmHg with a Tono-pen (SD ⬍5%, unknown time of day) O.D. and O.S. The cornea was clear in the left eye. The cornea of the right eye had some “faint horizontal lines,” which were attributed to old injuries to Descemet’s membrane rather than glaucoma. The corneal diameters measured 15 mm horizontally by 13 mm vertically O.D. and 12.5 mm horizontally by 12 mm vertically O.S. Pachymetry measured the right cornea thinner than the left; the right measured 517 m and the left was 560 m. A-scan ultrasonography found that the axial length was significantly longer for the right eye: 25.35 mm O.D. versus 22.07 mm O.S. A dilated fundus examination found “small cups” (no ratio stated) with the right slightly larger than the left. Gonioscopy was not deemed necessary. Based on the lack of classic signs and symptoms of glaucoma and normal IOP, the pediatric ophthalmologist diagnosed megalocornea O.D., with an atypical presentation because megalocornea is usually bilateral. The patient was instructed to return to our facility for follow-up care.
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Figure 2
Clinical Care
Oblique striae in Descemet’s layer of patient’s right cornea.
The patient returned 3 months later as scheduled to our facility for follow-up. The family had ordered the glasses previously prescribed but had not yet received them. The patient was now less fearful of the visual examination and, therefore, measurements were more reliable. Visual acuity was 20/63 O.D. and 20/32 O.S. with Teller preferential looking cards using the prescription lenses in a trial frame. Cover test found an intermittent right exotropia of approximately 25⌬ present 90% of the time at distance and approximately 15⌬ present 40% of the time at near. Extraocular muscle motilities were full OU. Dry retinoscopy showed no change in refractive error OU. Horizontal corneal diameters were measured at 15 mm O.D. and 12 mm O.S. At this visit, new oblique corneal striae were noted O.D. (see Figure 2). Noncontact tonometry was performed (because the patient was uncooperative for applanation), and IOP measured 21 mmHg O.D. and 15 mmHg O.S. at 10:30 AM. A dilated fundus examination found unchanged disc appearances with the previously noted asymmetry in cup-to-disc ratios. Because of the new corneal striae, the patient was referred again to the same pediatric ophthalmologist for evaluation. Additionally, a patching program was to be initiated as soon as the glasses were obtained to address the presumed anisometropic amblyopia O.D. The patient’s mother was instructed to patch the child’s left eye 2 to 3 hours per day with the glasses on while eye– hand coordination activities were performed. Some basic convergence therapy was instituted in the form of gross convergence exercises using no patch, to address the exotropia.11 The patient’s mother was instructed to return for a follow-up appointment at our facility in 2 months. An appointment was made for re-evaluation by the pediatric ophthalmologist in 1 month. The patient did not keep the appointment with the pediatric ophthalmologist but did return for a follow-up at our facility 3 months later. There were no changes in any of the findings. The patient was wearing his glasses only while watching television, and minimal patching and convergence exercises had been performed. The importance of patching and full-time wear of the spectacle correction was reiterated,
169 and a 2-month follow-up visit was planned to monitor home therapy, glasses wear, visual acuity, and frequency of exotropia. Three months later, the patient was re-evaluated under anesthesia. IOPs measured 22, 23, 21 mmHg O.D. and 25, 22 mmHg O.S. with a Tono-pen (SD ⬍5%) at 11:00 AM. The axial lengths were relatively unchanged at 25.11 mm LO.D. and 21.87 mmO.S. New, additional (since previous examination under anesthesia [EUA]), horizontal and oblique endothelial striae were noted in the right cornea, and the corneal measurements had enlarged to 18 mm horizontally by 14 mm vertically OD and 14 mm horizontally by 12 mm vertically OS. The optic nerve heads were unchanged since the previous visit. At this point, the pediatric ophthalmologist made a diagnosis of primary congenital (specifically, infantile) glaucoma because of the new corneal striae O.D., increase in corneal diameter OU, and slight increase in IOP OU compared with the previous examination. However, this diagnosis was made in the absence of gonioscopy. The pediatric ophthalmologist initiated treatment with Xalatan (Pfizer Ophthalmics, New York, New York) every evening O.D. to decrease the IOP. A follow-up examination was scheduled for 1 month, but the appointment was not kept. A few months later, the patient returned to our facility for a follow-up visit. The patient had worn the patch only rarely, but was using the Xalatan every night O.D. The patient also tolerated glasses more readily and wore them full time. Visual acuity and cover test results were stable. The family was reminded once again to continue with daily patching, to follow up with the pediatric ophthalmologist for continued monitoring of IOP under anesthesia, and to return 1 month later. Unfortunately, the patient was lost to follow-up, despite numerous attempts to contact the family. It became evident that the family had moved away.
Discussion In all types of pediatric glaucoma, the main goal of management is preservation of developing vision, not merely preservation of visual field as it is with adults. Primary congenital glaucoma has the best prognosis of all the pediatric glaucomas, with 52% to 79% of patients achieving visual acuity of 20/50 or better.6 There is no reversibility of the ocular enlargement because once the tissue has been stretched, it cannot shrink back to its original size.12 In contrast, when IOP is normalized, cupping of the optic nerve frequently can be reversed. This reversibility is possible because the optic disc tissues of an infant are not developed fully. As IOP increases, the optic nerve is compressed and moved posteriorly (because the collagenous tissues of the lamina cribrosa are not fully developed at birth), which allows the lamina to bow backward, reducing sustainable damage to the optic nerve head.13 In this case, the diagnosis was more elusive than usual, and the treatment was not standard. Before discussing this
170 case more specifically, we will review the diagnosis of more typical cases of primary congenital glaucoma.
Pathophysiology There are 2 predominant theories regarding the pathophysiology of primary congenital glaucoma. The first and most widely accepted theory is that primary congenital glaucoma is caused by “thickened beams” in the trabecular meshwork. This thickening leads to narrower trabecular spaces and reduced aqueous outflow. When such a child is born full term, the trabecular meshwork has not fully differentiated. Because of the immaturity of the trabecular meshwork at birth, there is developmental arrest of the iris, ciliary muscle, and anterior chamber angle. These structures appear as they normally would in the seventh month of gestation. Therefore, at birth, the iris, ciliary muscle, and anterior chamber angle end up in an anterior location that overlaps the trabecular meshwork, thereby also reducing aqueous outflow and preventing further differentiation of the trabecular meshwork.14-18 The second theory has as its basis a structure called Barkan’s membrane. Barkan’s membrane was thought to be an imperforate membrane that persisted after birth, covering the anterior chamber angle, thereby greatly reducing aqueous outflow. Reduced outflow would lead to increased IOP and congenital glaucoma. In recent years, this theory has been largely disproven because of the lack of histologic proof of this membrane.8,9 There has not been one truly accepted pathophysiology of congenital glaucoma.
Genetics Most commonly, primary congenital glaucoma presents in a sporadic fashion, although rarely is it hereditary. When it is hereditary, the condition is autosomal recessive with high penetrance and has been associated with abnormalities of 17 different chromosomes.6,19 Studies have located the cytochrome P4501B1 (CYP1B1) gene to be the main mutation site in congenital glaucoma, although it is unclear how this gene participates in the normal development of the eye.19
Signs and symptoms Typical anterior segment signs of primary congenital glaucoma consist of a well-established clinical triad: photophobia, blepharospasm, and epiphora. All of these clinical signs occur secondary to an increase in IOP, which stimulates corneal nerves and causes pain. Buphthalmos (ocular enlargement), corneal edema, and Haab’s striae (horizontal, diagonal, or curvilinear breaks in Descemet’s membrane) can occur as later signs if pressure is not controlled.20-22 Buphthalmos occurs because immature collagen remains distensible and leads to eye enlargement. Corneal edema and haze occur because of high pressure that compromises the endothelial hydrostatic pump mechanism.1 These signs
Optometry, Vol 78, No 4, April 2007 only occur during the first 3 years of life when the eye is still immature.8 However, Seidman et al.23 found that parents noted epiphora in only 55% of primary congenital glaucoma cases, photophobia and/or blepharospasm in 41%, corneal haze in 41%, and increased eye size in 32% of their cases. Corneal diameter should be approximately 10 mm at birth and 11 mm at 1 year of age, with an adult diameter of approximately 12 mm reached by 12 to 24 months of age.20 Posterior segment signs of primary congenital glaucoma are limited to the appearance of the optic nerve head. The increase in the size of the cup-to-disc ratio is more rapid in infants than in adults because of compression and posterior movement of tissues within the optic nerve head.13 There have been few studies measuring IOP in children without pathologic findings; therefore, no normative values have been standardized. However, it is known that IOP in the first year of life is much lower than that of an adult and that anesthesia generally lowers IOP.1 It has been proven that the normal IOP for children is at its lowest in newborns and increases with age; however, clinicians should note that any IOP from 17 to 20 mmHg is suspicious for congenital glaucoma before the age of 4 years.24 The IOP in congenital glaucoma often is considered only moderately elevated and should not be heavily relied on, as opposed to the attention given to IOP in adult glaucoma, in which it is often significantly elevated.1 When instrumentation is considered, Goldmann applanation tonometry is the “gold standard” but is difficult to obtain in many children without sedation. Hand-held tonometers are generally easier to use in children. The Perkins tonometer is considered to be the “gold standard” of portable tonometers, because Perkins is an applanation tonometer, and there have been studies illustrating the close correlation between the Goldmann tonometer and the Perkins tonometer.25 Additionally, several studies have compared Goldmann tonometry and tonometry with a Tono-pen. Tono-pen measurements with SD ⬍5% of the mean of 4 measurements correspond well to Goldmann measurements in the 11- to 20-mmHg range, reasonably well in the 21- to 30-mmHg range, and poorly over 30 mmHg. Overall, the consensus is that use of a Tono-pen is not recommended in the IOP range greater than 21 mmHg.26-28 Noncontact tonometry (NCT) can also be used on children. When reliability between NCT and Goldmann is studied, results indicate poor correlation for pressures in the 20- to 30-mmHg range but good correlation for pressures more than 30 mmHg. NCT is more useful as an IOP screening tool or when applanation tonometry is unobtainable in a child.29
Differential diagnoses When the primary congenital glaucoma triad of photophobia, epiphora, and blepharospasm, as well as any additional clinical signs, are present, it is critical to first rule out a number of other conditions. When buphthalmos is suspected, there are 2 main differentials: megalocornea and high myopia. Megalocornea is a rare, nonprogressive, gen-
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erally bilateral corneal enlargement. The corneal enlargement to 13 mm diameter or larger is present from birth. Ninety percent of cases are in males because of the X-linked recessive inheritance. Megalocornea is characterized by large, clear corneas, normal IOP, no Haab’s striae, no buphthalmos, and no pathologic optic nerve head cupping.30 Indeed, rarely, cases of simple megalocornea have been known to progress to glaucoma.31 High myopia is also accompanied by clear, normally sized corneas and normal IOP. The optic nerve head may have a normal appearance or possibly be tilted. High myopia may show other characteristic fundus signs such as scleral crescent and choroidal mottling. A cloudy cornea may be caused by birth trauma, corneal dystrophy, interstitial keratitis, metabolic disease, or anterior chamber malformation. Birth trauma, corneal dystrophy, metabolic disease, and anterior chamber malformation are apparent soon after birth. Metabolic diseases, such as Lowe’s syndrome, mucopolysaccharidosis, and cystinosis, have other systemic symptoms associated as well. Interstitial keratitis is associated with red eyes and corneal stromal blood vessels.1,8,32 When a child presents with tearing, there are 5 main conditions to rule out: congenital nasolacrimal duct obstruction, conjunctivitis, anterior uveitis, corneal abrasion/corneal foreign body, and keratoconjunctivitis sicca. Congenital nasolacrimal duct obstruction is also associated with mucopurulent discharge and matting of the eyelashes. Conjunctivitis is associated with red, inflamed eyes and possible discharge. Anterior uveitis is accompanied by photophobia, conjunctival injection, and anterior chamber cells and flare. When a corneal abrasion or foreign body is suspected, the patient is usually in pain, and corneal staining and a good history can make the definitive diagnosis. Keratoconjunctivits sicca, although uncommon in children, is a diagnosis of exclusion in cases of tearing eyes and can be determined by corneal staining, punctate corneal erosions, or reduced tear breakup time.1,32 Photophobia can be caused by corneal abrasion, foreign body, interstitial keratitis, anterior uveitis, achromatopsia, hypopigmentation syndromes (e.g., albinism), or even intermittent exotropia/high exophoria. Generally, systemic diseases are associated with cases of interstitial keratitis and anterior uveitis. Diseases such as syphilis, juvenile rheumatoid arthritis, Lyme disease, tuberculosis, and sarcoid should be considered and referral to the child’s pediatrician for a full blood workup initiated. Achromatopsia (rod monochromatism) is characterized by varying degrees of color deficiency, poor central vision, nystagmus, and pigmentary macular changes and presents bilaterally. Also presenting bilaterally, ocular albinism results in very light fundi, iris transillumination defects, and displays of visible choroidal vasculature.1,32 Blepharospasm can be caused by keratoconjunctivitis sicca, foreign body, or a neurological tic (in a patient with healthy eyes).1,32 Blepharospasm can also be related to
171 seventh cranial nerve complications or Tourette’s syndrome.32 Other common causes of primary glaucoma include such conditions as Axenfeld-Rieger syndrome, Peter’s anomaly, Sturge-Weber syndrome, neurofibromatosis, and aniridia. These diagnoses can be made on observation of the associated ocular and systemic anomalies.6
Analysis of current case In this case, the patient’s parents did not recall symptoms of tearing, photophobia, or blepharospasm. Initial examination found an enlarged right cornea, right exotropia, unilateral high myopia, a cup-to-disc ratio that was larger in the right eye than the left, and clear corneas. The bilaterally elevated intraocular pressures were considered questionable because of the patient’s inability to tolerate the examination, but the unilateral ocular enlargement warranted referral for an EUA by a pediatric ophthalmologist to rule out glaucoma. The EUA confirmed the unilateral ocular enlargement, but IOP was found to be only modestly elevated at that time. This could in part be caused by the use of a Tono-pen for measurement. Thus, the few horizontal striae noted O.D., only by initial evaluation of the ophthalmologist, were attributed to injury. This asymptomatic child was considered to have a rare case of unilateral megalocornea. The subsequent optometric examination 3 months later found newly noted, obliquely oriented striae and a higher IOP O.D., necessitating a second EUA. Because this EUA confirmed multiple new corneal striae O.D., additional corneal enlargement, and slightly elevated IOP bilaterally, the ophthalmologist rediagnosed the case as primary congenital (infantile) glaucoma and began treatment with latanoprost. Further follow-up would have allowed us to determine if his IOP responded adequately to this conservative medical management or if surgical intervention would become necessary to prevent further glaucomatous damage. There are some diagnostic limitations of the case presented. Gonioscopy was not performed by the ophthalmologist during the EUA. This omission was beyond our control. It would also have been preferable had the ophthalmologist used a more accurate method of determining IOP during the EUA. In cases of primary congenital glaucoma, gonioscopy is helpful not only to make the diagnosis of specific glaucoma type but to properly direct the patient toward definitive surgical treatment. The angle of a patient with primary congenital glaucoma may appear nearly normal with only slightly anterior iris insertion and a subtly different translucency of the trabecular meshwork. When the angle structures are still not fully differentiated, it can be challenging to label them as normal or abnormal.8 In cases in which there is markedly elevated IOP, cloudy corneas, and the classical symptomatic triad, gonioscopy is perhaps unnecessary. In this atypical situation, gonioscopy would have been extremely helpful in making the diagnosis. However,
172 based on the preponderance of evidence, this case can be diagnosed as primary congenital glaucoma. Although rare, spontaneous resolution of primary congenital glaucoma cases with no surgical treatment or minimal medical therapy has been reported by Lockie and Elder.33 Considering that not all cases of primary congenital glaucoma result in the classic symptoms, it is possible that this patient did not experience symptoms because his condition may have been less severe.23 A second EUA found new striae, elevated IOPs (for a patient of this age), and further corneal enlargement. It is possible that this patient may have had a relatively mild case of primary congenital glaucoma, affecting mainly the right eye. Although megalocornea was included in the differential, it is highly unlikely because continued corneal enlargement and new corneal striae were noted at the second EUA, which had not been seen at the first EUA. Certainly, the level of IOP in a child of this age with possible changes suggestive of infantile glaucoma clearly dictated intervention. Although very uncommon, this case clearly showed variability during the period of follow-up. Unfortunately, because this patient was lost to long-term follow-up, his future visual prognosis is uncertain. Nevertheless, the prognosis is not likely to be good without continued treatment. Of note, the presence of anisometropic amblyopia in a highly myopic eye (with anisometropia greater than 3 to 4 D), along with ipsilateral exotropia is fairly common and not necessarily attributable to glaucoma.34,35 Also noteworthy, 31% of a sample of patients with primary congenital glaucoma showed at least 2.00 D of anisometropia, and it is reported that 100% of patients have at least this degree of anisometropia if unilateral primary congenital glaucoma is diagnosed.12,50 In the presented case, we believe that glaucomatous ocular enlargement of the right eye was the underlying cause of the anisometropia that led to amblyopia and secondary exotropia. Amblyopia is common in cases of congenital glaucoma, often resulting from form deprivation (cloudy cornea), although not a factor in the current case.6 The amblyopia treatment attempted consisted of commonly used part-time, opaque, direct occlusion and eye-hand coordination activities to stimulate visual development.11 The exotropia treatment, which was limited by age, consisted of basic gross convergence exercises.
Treatment of primary congenital glaucoma Primary congenital glaucoma is better treated with surgery than medication because of the pathophysiology of the disease. Little research has been done in the area of medical management, because drugs are not often used in these cases. Generally, there are 2 indications for use of glaucoma medications in primary congenital glaucoma: before surgery, either to constrict the pupil (miotics) or to lower the IOP or as a supplement to surgery to further decrease the IOP. However, Turach et al.36 found that IOP-lowering medications adequately controlled IOP long term without surgery in approximately 10% of their cases, and Barsoum-
Optometry, Vol 78, No 4, April 2007 Homsy and Chevrette37 found control in 4% of their cases. When medical treatment is initiated, the main medications used are timolol, dorzolamide, and latanoprost.38 Timolol is a good single treatment drug when used for mild glaucoma in children but does not have the same IOP-lowering effects as a single-use drug in severe glaucoma.39,40 Reports of timolol’s usefulness when added to other medications are varied, but the overall consensus is that timolol does have additional IOP-lowering effects when used with other medications.6,39,40 It is generally not prescribed for children younger than 2 years of age because of the potential for cardiac side effects secondary to systemic absorption. Timolol has the best efficacy in patients who are at least 9 years of age.6,40 The main contraindications for pediatric timolol use include asthma, congestive heart failure, and bradycardia. The side effects are apnea, bradycardia, hypotension, increase in asthma, reduced heart rate, dissociative behavior, drowsiness, tearing, eye itching, and lightheadedness. It is rare for any of these side effects to become so severe that a patient needs to discontinue timolol therapy.39-43 One study found that use of topical timolol did reach beta blockade levels in children less than 2 years of age, but another did not find these results.21,40 Multiple studies have found that oral carbonic anhydrase inhibitors (CAIs, specifically, acetazolamide) produce more IOP reduction than topical CAIs (dorzolamide). Oral CAIs are used infrequently in children because of a much higher incidence of side effects than in adults.44 Side effects include allergy, gastrointestinal disturbance, paresthesia, and metabolic acidosis.38 Side effects reported from use of topical CAIs include taste perversion, headaches, upper respiratory tract infections, ocular burning/stinging, and ocular hyperemia.45 Topical CAIs are an effective first- or second-line medical treatment. The IOP reduction rate of topical dorzolamide has been reported to vary from 14% to 36%.44,46 Latanoprost is systemically safer than timolol and dorzolamide but has a greater nonresponse rate. Latanoprost causes only rare side effects, including conjunctival redness and irritation. This medication is not as effective in children as it is in adults and has its best IOP-reducing effects on juvenile open-angle glaucoma.47 Adrenergic agonists are rarely used because of severe potential side effects, most notably effects on the central nervous system causing severe fatigue and drowsiness. It is unclear why the ophthalmologist treating this patient chose latanoprost over surgery or the first-line medical treatment (timolol) for a case diagnosed as primary congenital glaucoma. Many surgical options exist for treatment of primary congenital glaucoma. The procedures performed with the best success on children are different than those for adults because of the differences in pathophysiology of the disease in adults and children.1,6,48 Overall, the best success rate with surgery occurs when done by the age of 3 years. Goniotomy and trabeculotomy are the procedures most commonly performed on children and have the best success
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rates.37,48 Both of these procedures restore physiologic outflow from the anterior chamber angle.1 Goniotomy involves using a needle, knife, or laser to make an incision into the anterior aspect of the middle third of the trabecular meshwork over 360°.48,49 The success rate is 70% to 90%, if done in the first 2 years of life, and success can generally be determined within a 6-month postoperative period.50 As a child becomes older than 2 years, the trabecular meshwork becomes more collagenous, and this procedure becomes less useful.51 The success of goniotomy is not limited by duration of the disease or level of intraocular pressure before treatment.50 The main limitation to this procedure is corneal clarity. When the cornea is cloudy, this procedure cannot be performed without an endoscope to better visualize the angle. Also noteworthy, if the cornea is clear, the success rate is the same, independent of corneal size.6,12,49,50,52 The main complications of goniotomy include self-limited hyphema, iridodialysis, cyclodialysis, and localized Descemet’s detachment.9 About 25% of patients who have undergone goniotomy require retreatment.50,53 Trabeculotomy involves an external dissection of Schlemm’s canal, with a metal probe inserted and rotated into the anterior chamber inferotemporally. Between 100° and 360° of the angle are treated; this decision is entirely dependent on the surgeon and his or her comfort and experience with the procedure.48,51 Trabeculotomy creates a direct continuity between Schlemm’s canal and the anterior chamber. Complications are similar to goniotomy. Trabeculotomy can be performed with a cloudy cornea because there is less need to visualize the angle than with goniotomy. Success rates for trabeculotomy have been reported by some sources to be better than for goniotomy, but generally it is accepted that the success rates are equal.54,55 If goniotomy or trabeculotomy fails the first time, a patient can be retreated a second time with a good success rate. If after this second treatment the glaucoma is still uncontrolled, then other procedures are generally performed.37 Uncontrolled glaucomatous optic nerve damage and amblyopia are the main reasons for postsurgical poor vision.6 Filtration or trabeculectomy is a second-line procedure if goniotomy or trabeculotomy fails.56,57 However, trabeculectomy becomes the first choice for treatment if the patient is older than 3 years because of the aforementioned physiologic changes that the eye goes through around the 2- to 3-year mark.8,48,58 Trabeculectomy is more often used outside the United States at any age because the surgeons have limited goniotomy/trabeculotomy experience. Trabeculectomy can be performed despite a cloudy cornea.58,59 There is more failure with trabeculectomy than goniotomy or trabeculotomy because of complications (including scarring over the bleb). Therefore, adjunctive therapy is generally used in the form of antifibrotic agents like mitomycin C, 5-fluoruracil, or betairradiation. Mitomycin C produces more ocular side effects than the milder 5-fluorouracil and beta-irradiation.1,58 Varying reports exist of use of these antifibrotic agents and success rates
173 (IOP control) with and without these products.6,49,58,59 The general consensus among surgeons is to incorporate antifibrotics; doing so yields an average 60% success rate for filtration surgery. When these agents are not incorporated, the success rate is drastically lower at 30% to 35%. Regardless of whether adjunctive antifibrotic agents are used, there are more complications with trabeculectomy than with goniotomy or trabeculotomy, most important bleb-related endophthalmitis.6,59 Other surgical procedures for treatment of infantile glaucoma include a combined trabeculotomy–trabeculectomy, aqueous shunting, and cyclodestruction. The combined trabeculotomy–trabeculectomy procedure has varying results. There is potential for more complications with the combined procedure than with a single procedure.6,51,60 The most common aqueous shunt device is the Molteno valve. Aqueous shunting also requires adjunctive therapy, like trabeculectomy, to decrease fibrosis and tissue adhesions around the implant area. Aqueous shunting has many complications, most of which relate to the implant, and is only used if other surgical procedures fail.6,56 Cyclodestruction is the procedure of last resort, reserved for children with a poor visual prognosis or those who have had multiple failed surgeries. It is unpopular because of the low success rate and frequent need for retreatment. Cyclodestruction also has a high rate of complications, which are more severe than those of the other surgical procedures.1,6,48,61
Conclusion Primary congenital glaucoma is a sight-threatening disease. This condition commonly presents with a clinical triad of photophobia, epiphora, and blepharospasm. It is important that eye care providers be aware of the clinical signs. The presence of a unilateral or bilateral enlarged cornea is another indication to investigate for glaucoma in a child, even without the classic signs. Management may include medical, surgical, optical, and amblyopia treatment. Medical treatment is rarely initiated because of the poor response rate of primary congenital glaucoma. Surgical treatment is the best option because of the pathophysiology of the disease, with either goniotomy or trabeculotomy as the first choice. Amblyopia is a common secondary condition, which, if untreated, may be sight threatening as well. Appropriate optical correction and protective eyewear are important for optimal visual function. The combined efforts of ophthalmic professionals are required to attain the best visual acuity for these patients. Primary congenital glaucoma has a good visual outcome in many cases when there is adequate IOP control and appropriate management of accompanying conditions.
Acknowledgments The authors thank Sandra Block, O.D., M.Ed., Christine Allison, O.D., and Michelle Chan, O.D., for their helpful
174 comments on earlier versions of this manuscript. This case was presented as a poster at the 2004 Annual Meeting of the American Academy of Optometry in Tampa, Florida.
References 1. Rubin S, Marcus C. Glaucoma in childhood. Pediatric Ophthalmology, The Ophthalmology Clinics of North America 1996;9:215-6. 2. Genick A. Epidemiology and genetics of primary congenital glaucoma in Slovakia: Description of a form of primary congenital glaucoma in gypsies with autosomal recessive inheritance and complete penetrance. Dev Ophthalmol 1989;16:75-115. 3. Francois J. Heredity in ophthalmology. St. Louis: Mosby; 1961:218-25. 4. Francois J. Congenital glaucoma and its inheritance. Ophthalmologica 1972;181:61-73. 5. Basic and clinical science course, section 10, glaucoma 1993-1994. San Francisco: American Academy of Ophthalmology, 1993. 6. Beck A. Diagnosis and management of pediatric glaucoma. Pediatric Ophthalmology, The Ophthalmology Clinics of North America 2001; 14:501-12. 7. Kanski JJ. Clinical ophthalmology, 4th ed. Boston: ButterworthHeinemann, 1999;143, 235-8. 8. DeLuise VP, Anderson DR. Primary infantile glaucoma (congenital glaucoma). Surv Ophthalmol 1983;28:1-19. 9. Barkan O. Technic of goniotomy. Arch Ophthalmol 1938;19:217-23. 10. Frantz KA, Peters RJ, Maino DM, et al. Effect of resisting tonometry on intraocular pressure. J Am Optom Assoc 1994;65:732-6. 11. Caloroso EE, Rouse MW. Clinical management of strabismus. Boston: Butterworth-Heinemann, 1993. 12. Robin AL, Quigley HA, Pollack IP, et al. An analysis of visual acuity, visual fields, and disk cupping in childhood glaucoma. Am J Ophthalmol 1979;88:847-58. 13. Quigley HA. The pathogenesis of reversible cupping in congenital glaucoma. Am J Ophthalmol 1977;84:358-70. 14. Anderson DR. The development of the trabecular meshwork and its abnormality in primary infantile glaucoma. Trans Am Ophthalmol Soc 1981;79:458-85. 15. Trachimowicz R. Review of embryology and its relation to ocular disease and the pediatric population. Optom Vis Sci 1994;71:154-63. 16. Tawara A, Inomata H. Congenital abnormalities of the trabecular meshwork in primary glaucoma with open angle. Glaucoma 1987;9: 28-34. 17. Arora R, Aggarwal HC, Sood NN. Observations on the histopathology of trabecular meshwork with reference to the pathogenesis of congenital glaucoma. Glaucoma 1990;12:112-6. 18. Maumenee AE. Further observations on the pathogenesis of congenital glaucoma. Am J Ophthalmol 1963;55:1163-76. 19. Safarazi M, Stoilov I. Molecular genetics of primary congenital glaucoma. Eye 2000;14:422-8. 20. Isenberg S. The eye in infancy, 2nd ed. St. Louis: Mosby; 1993:64, 301. 21. Hoskins HD, Kass M. Becker-Shaffer’s diagnosis and therapy of the glaucomas, 6th ed. St. Louis: CV Mosby, 1989;364-5. 22. Chandler PA, Grant WM. Lectures on glaucoma. Philadelphia: Lea & Febiger, 1965;312-3. 23. Seidman DJ, Nelson LB, Calhoun JH, et al. Signs and symptoms in presentation of primary infantile glaucoma. Pediatrics 1986;77:399-404. 24. Pensiero S, Da Pozzo S, Perissutti P, et al. Normal intraocular pressure in children. J Pediatr Ophthalmol Strabismus 1992;29:79-84. 25. Garcia-Resua C, Gonzalez-Meijome JM, Gilino J, et al. Accuracy of the new ICare rebound tonometer vs. other portable tonometers in healthy eyes. Optom Vis Sci 2006;83:102-7. 26. Wingert TA, Bassi CJ, McAlister WH, et al. Clinical evaluation of five portable tonometers. J Am Optom Assoc 1995;66:670-4. 27. Armstrong TA. Evaluation of the Tono-Pen and the Pulsair tonometers. Am J Ophthalmol 1990;109:716-20.
Optometry, Vol 78, No 4, April 2007 28. Frenkel REP, Hong YJ, Shin DH. Comparison of the Tono-Pen to the Goldmann applanation tonometer. Arch Ophthalmol 1988;106:750-3. 29. Lagerlöf O. Airpuff tonometry versus applanation tonometry. Acta Ophthalmol 1990;68:221-4. 30. Oetting TA, Hendrix MA. Megalocornea (emedicine database). Available at: http://www.emedicine.com/oph/topic549.htm. Last accessed June 18, 2006. 31. Kluyskens J. Le glaucome congenital. Bull Soc Belg Ophthalmol 1950;94:10,194-5. 32. Rhee D, Ryfer M. The Wills eye manual, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 1999. 33. Lockie P, Elder J. Spontaneous resolution of primary congenital glaucoma. Aust NZ J Ophthalmol 1989;17:75-7. 34. Tanlamai T, Goss DA. Prevalence of monocular amblyopia among anisometropic amblyopes. Am J Optom Physiol Opt 1979;56:704-15. 35. Rouse MW, Cooper JS, Cotter SA, et al. Optometric clinical practice guideline: care of the patient with amblyopia. St. Louis: American Optometric Association, 1994;5-7. 36. Turach ME, Gülderen A, Aysun I. Medical and surgical aspects of congenital glaucoma. Acta Ophthalmol Scand 1995;73:261-3. 37. Barsoum-Homsy M, Chevrette L. Incidence and prognosis of childhood glaucoma: A study of 63 cases. Ophthalmology 1986;93:1323-7. 38. Talbot AWR, Russell-Eggit I. Pharmaceutical management of the childhood glaucomas. Exp Opin Pharmacother 2000;1:697-711. 39. Boger W, Walton D. Timolol in uncontrolled childhood glaucomas. Ophthalmology 1981;88:253-8. 40. McMahon C, Hetherington J, Hoskins H, et al. Timolol and the pediatric glaucomas. Ophthalmology 1981;88:249-52. 41. Zimmerman T, Kooner K, Morgan K. Safety and efficacy of timolol in pediatric glaucoma. Surv Ophthalmol 1983;28:262-4. 42. Hoskins H, Hetherington J, Magee S, et al. Clinical experience with timolol in childhood glaucoma. Arch Ophthalmol 1985;103:1163-5. 43. Olson RJ, Bromberg BB, Zimmerman TJ. Apneic spells associated with timolol therapy in a neonate. Am J Ophthalmol 1979;88:120-2. 44. Protellos M, Buckley EG, Freedman SF. Topical versus oral carbonic anhydrase inhibitor therapy for pediatric glaucoma. J AAPOS 1998; 2:43-7. 45. Ott EZ, Mills MD, Arango S, et al. A randomized trial assessing dorzolamide in patients with glaucoma who are younger than 6 years. Arch Ophthalmol 2005;123:1177-86. 46. Enyedi LB, Freedman SF. Safety and efficacy of brimonidine in children with glaucoma. J AAPOS 2001;5:281-4. 47. Enyedi L, Freedman S, Buckley E. The effectiveness of latanoprost for the treatment of pediatric glaucoma. J AAPOS 1999;3:33-9. 48. Wilson R. Changes in surgical care of pediatric glaucoma. Rev Ophthalmol 2002;9(2):82-5. 49. Sun W, Shen J, Shetlar D, et al. Endoscopic goniotomy with the free electron laser in congenital glaucoma rabbits. J Glaucoma 2000;9: 325-33. 50. Broughton WL, Parks MM. An analysis of treatment of congenital glaucoma by goniotomy. Am J Ophthalmol 1981;91:566-72. 51. Mandal A, Naduvilath T, Jayagandan A. Surgical results of combined trabeculotomy-trabeculectomy for developmental glaucoma. Ophthalmology 1998:105:974-82. 52. Joos KM, Alward WLM, Folberg R. Experimental endoscopic goniotomy: A potential treatment for primary infantile glaucoma. Ophthalmology 1993;100:1066-70. 53. Russell-Eggitt IM, Rice NSC, Jay B, et al. Relapse following goniotomy for congenital glaucoma due to trabecular dysgenesis. Eye 1992;6:197-200. 54. Akimoto M, Tanihara H, Negi A, et al. Surgical results of trabeculotomy ab externo for developmental glaucoma. Arch Ophthalmol 1994;112:1540-4. 55. McPherson SD, McFarland D. External trabeculotomy for developmental glaucoma. Ophthalmology 1980;87:302-5. 56. Pereira M, Araujo S, Wilson R, et al. Aqueous shunts for intractable glaucoma in infants. Ophthal Surg Lasers 2002;33:19-29.
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57. Gressel MG, Heuer DK, Parrish II RK. Trabeculectomy in young patients. Ophthalmology 1984;91:1242-6. 58. Khaw P. What is the best primary surgical treatment for the infantile glaucomas? Br J Ophthalmol 1996;80:495-6. 59. Dureau P, Dollfus H, Cassegrain C, et al. Long-term results of trabeculectomy for congenital glaucoma. J Pediatr Ophthalmol Strabismus 1998;35:198-202.
175 60. Mandal A, Bhatia P, Gothwal V, et al. Safety and efficacy of simultaneous bilateral primary combined trabeculotomy-trabeculectomy for developmental glaucoma. Indian J Ophthalmol 2002; 50:13-9. 61. Al Faran MF, Tomey KF, Al Mutlaq FA. Cyclocryotherapy in selected cases of congenital glaucoma. Ophthal Surg 1990;21:794-8.
A case of primary congenital glaucoma: A diagnostic dilemma Nadine M. Girgis, O.D.,a,b and Kelly A. Frantz, O.D.b a
Northwest Optometric Associates, Harwood Heights, Illinois, and bIllinois College of Optometry, Chicago, Illinois. KEYWORDS Congenital glaucoma; Buphthalmos; Goniotomy; Trabeculotomy; Trabeculectomy; Amblyopia; Haab’s striae
Abstract BACKGROUND: Primary congenital glaucoma generally presents with a classic clinical triad of photophobia, blepharospasm, and epiphora caused by the corneal changes that occur secondary to increased intraocular pressure (IOP). The condition typically presents bilaterally and is rarely hereditary. Onset is from age 2 months to 2 to 3 years. CASE REPORT: A 2-year, 5-month-old Hispanic boy presented with an enlarged right eye and an intermittent right exotropia, without tearing or photophobia. Examination also found high myopia and an optic nerve cup-to-disc ratio larger in the right than the left eye. Referral to a pediatric ophthalmologist was initiated. On the first examination under anesthesia (EUA), the child was diagnosed with unilateral megalocornea with a normal IOP. He did not have any other typical signs and symptoms of primary congenital glaucoma. An EUA 8 months later led to a diagnosis of primary congenital glaucoma based on the new appearance of Haab’s striae, further enlargement of the cornea, and an elevated IOP. At this point, medical management was instituted. CONCLUSION: This case shows the importance of recognizing signs of primary congenital glaucoma so that appropriate management can begin as soon as possible to provide the best visual outcome for a child. Optometry 2007;78:167-175
Pediatric glaucoma is a broad category that includes any type of glaucoma, primary or secondary, presenting from birth to 18 years of age. The primary pediatric glaucomas are caused by congenital anomalies that affect aqueous outflow. Secondary pediatric glaucomas are caused by postbirth factors such as ocular trauma, surgery, and inflammation. The primary pediatric glaucomas are more common than the secondary glaucomas.1 Primary congenital glaucoma occurs in 1 in 10,000 children in the United States. This prevalence rate is quoted as the world average, although specific prevalence rates vary for different populations around the world from 1 in 1,250 to 1 in 22,000.2-4
Corresponding author: Nadine M. Girgis, O.D., Northwest Optometric Associates, 4970 N Harlem Avenue, Harwood Heights, Illinois 60706. E-mail: [email protected]
Seventy percent of these cases are bilateral, and 65% of the children affected are male.5 Primary pediatric glaucoma consists of many types of glaucoma, of which primary congenital glaucoma is the most prevalent. Primary congenital glaucoma consists of 3 subcategories that are categorized by age of onset, although generally in the literature the 3 types are not delineated, and are simply grouped under the term primary congenital glaucoma.1 Primary congenital glaucoma (40%) presents from birth to age 2 months. Primary infantile glaucoma (55%) presents from age 2 months to 2 or 3 years.6,7 Late-onset primary infantile glaucoma presents after 3 years of age. Juvenile-onset primary open-angle glaucoma presents anywhere from childhood into early adulthood. Primary congenital, infantile, and late-onset infantile glaucoma are caused by an isolated anomaly of the trabecular mesh-
1529-1839/07/$ -see front matter © 2007 American Optometric Association. All rights reserved. doi:10.1016/j.optm.2006.10.016
168 work (trabeculodysgenesis). For the remainder of this discussion, congenital, infantile, and late-onset infantile glaucoma all will be labeled primary congenital glaucoma because that is how they are commonly referred to in the literature. Juvenile-onset primary open-angle glaucoma is not caused by trabeculodysgenesis and presents as adult primary open-angle glaucoma. Like adult primary openangle glaucoma, the juvenile variety has an unknown pathophysiology.8,9 Primary congenital glaucoma generally presents with a classic clinical triad of photophobia, blepharospasm, and epiphora. These signs are caused by the corneal changes that occur secondary to increased intraocular pressure (IOP). Because the young eye is still distensible, high IOP can lead to enlargement of the eye, breaks in Descemet’s membrane (Haab’s striae), and stromal edema causing a cloudy cornea and optic nerve damage.1 Primary congenital glaucoma is a vision-threatening disease. Therefore, it is important to understand the signs, symptoms, and treatment for optimal management of patients. By no means is pediatric glaucoma a straightforward disease. This report presents an atypical case of congenital glaucoma with an elusive diagnosis and reviews potential differential diagnoses and treatment considerations once the disease is diagnosed.
Case A 2-year, 5-month-old Hispanic boy presented to our facility for his first eye examination. His mother brought him because she had noticed that his right eye was larger than his left eye, and his right eye intermittently turned out. Inspection of photographs supplied by the mother showed evidence of a larger right eye in pictures taken at age 8 months, but not in one taken at age 1 month (no photographs were available showing the patient at other ages). The mother denied noticing tearing or photophobia. The patient’s ocular history revealed no trauma or surgery to either eye. The patient’s medical history was unremarkable, and he used no medications. His family history was negative for glaucoma or strabismus. The patient was hesitant and uncooperative throughout the examination, although he did not appear to be experiencing any pain. He did not respond to visual acuity testing with Teller preferential looking acuity cards beyond the 20/1200 in both eyes (OU) level and did not allow occlusion of either eye. Pupils were equal, round, and reactive to light OU, without an afferent pupillary defect. Extraocular muscle motility was full for both eyes. Cover test found an intermittent right exotropia of approximately 25⌬ at distance, orthophoria at near, and no vertical component. Anterior segment evaluation found a corneal diameter of 14 mm horizontally in the right eye (O.D.) and 12 mm horizontally in the left eye (O.S.) (see Figure 1). The child showed no photophobia or tearing. Neither corneal edema
Optometry, Vol 78, No 4, April 2007
Figure 1
Patient with right eye noticeably larger than the left at 3
years of age.
nor Haab’s striae were apparent. IOP was measured as 33, 37 mmHg O.D. and 33, 33 mmHg O.S. at 11:15 AM with a Tono-pen (Medtronic, Jacksonville, Florida) (with standard deviation [SD] less than 5% of the mean of 4 measurements). However, the patient was very agitated and uncooperative, which may have led to inaccurately higher readings.10 Postdilation retinoscopy found a ⫺5.00 diopter (D) sphere O.D., and plano O.S. The optic nerve had a cup-todisc ratio of 0.5 horizontally and vertically O.D. and 0.4 horizontally and vertically O.S. with apparently healthy rim tissue OU. A prescription was given of O.D. ⫺5.00 D sphere and O.S. plano in polycarbonate lenses for full-time wear. Based on the findings of anisometropia, unequal optic nerve appearance, the right corneal diameter larger than the left, and suspicious IOPs, referral to a pediatric ophthalmologist was instituted to rule out congenital glaucoma versus unilateral megalocornea. Two months later, the pediatric ophthalmologist performed an examination under anesthesia to obtain more accurate objective findings. IOP was 19 mmHg with a Tono-pen (SD ⬍5%, unknown time of day) O.D. and O.S. The cornea was clear in the left eye. The cornea of the right eye had some “faint horizontal lines,” which were attributed to old injuries to Descemet’s membrane rather than glaucoma. The corneal diameters measured 15 mm horizontally by 13 mm vertically O.D. and 12.5 mm horizontally by 12 mm vertically O.S. Pachymetry measured the right cornea thinner than the left; the right measured 517 m and the left was 560 m. A-scan ultrasonography found that the axial length was significantly longer for the right eye: 25.35 mm O.D. versus 22.07 mm O.S. A dilated fundus examination found “small cups” (no ratio stated) with the right slightly larger than the left. Gonioscopy was not deemed necessary. Based on the lack of classic signs and symptoms of glaucoma and normal IOP, the pediatric ophthalmologist diagnosed megalocornea O.D., with an atypical presentation because megalocornea is usually bilateral. The patient was instructed to return to our facility for follow-up care.
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Figure 2
Clinical Care
Oblique striae in Descemet’s layer of patient’s right cornea.
The patient returned 3 months later as scheduled to our facility for follow-up. The family had ordered the glasses previously prescribed but had not yet received them. The patient was now less fearful of the visual examination and, therefore, measurements were more reliable. Visual acuity was 20/63 O.D. and 20/32 O.S. with Teller preferential looking cards using the prescription lenses in a trial frame. Cover test found an intermittent right exotropia of approximately 25⌬ present 90% of the time at distance and approximately 15⌬ present 40% of the time at near. Extraocular muscle motilities were full OU. Dry retinoscopy showed no change in refractive error OU. Horizontal corneal diameters were measured at 15 mm O.D. and 12 mm O.S. At this visit, new oblique corneal striae were noted O.D. (see Figure 2). Noncontact tonometry was performed (because the patient was uncooperative for applanation), and IOP measured 21 mmHg O.D. and 15 mmHg O.S. at 10:30 AM. A dilated fundus examination found unchanged disc appearances with the previously noted asymmetry in cup-to-disc ratios. Because of the new corneal striae, the patient was referred again to the same pediatric ophthalmologist for evaluation. Additionally, a patching program was to be initiated as soon as the glasses were obtained to address the presumed anisometropic amblyopia O.D. The patient’s mother was instructed to patch the child’s left eye 2 to 3 hours per day with the glasses on while eye– hand coordination activities were performed. Some basic convergence therapy was instituted in the form of gross convergence exercises using no patch, to address the exotropia.11 The patient’s mother was instructed to return for a follow-up appointment at our facility in 2 months. An appointment was made for re-evaluation by the pediatric ophthalmologist in 1 month. The patient did not keep the appointment with the pediatric ophthalmologist but did return for a follow-up at our facility 3 months later. There were no changes in any of the findings. The patient was wearing his glasses only while watching television, and minimal patching and convergence exercises had been performed. The importance of patching and full-time wear of the spectacle correction was reiterated,
169 and a 2-month follow-up visit was planned to monitor home therapy, glasses wear, visual acuity, and frequency of exotropia. Three months later, the patient was re-evaluated under anesthesia. IOPs measured 22, 23, 21 mmHg O.D. and 25, 22 mmHg O.S. with a Tono-pen (SD ⬍5%) at 11:00 AM. The axial lengths were relatively unchanged at 25.11 mm LO.D. and 21.87 mmO.S. New, additional (since previous examination under anesthesia [EUA]), horizontal and oblique endothelial striae were noted in the right cornea, and the corneal measurements had enlarged to 18 mm horizontally by 14 mm vertically OD and 14 mm horizontally by 12 mm vertically OS. The optic nerve heads were unchanged since the previous visit. At this point, the pediatric ophthalmologist made a diagnosis of primary congenital (specifically, infantile) glaucoma because of the new corneal striae O.D., increase in corneal diameter OU, and slight increase in IOP OU compared with the previous examination. However, this diagnosis was made in the absence of gonioscopy. The pediatric ophthalmologist initiated treatment with Xalatan (Pfizer Ophthalmics, New York, New York) every evening O.D. to decrease the IOP. A follow-up examination was scheduled for 1 month, but the appointment was not kept. A few months later, the patient returned to our facility for a follow-up visit. The patient had worn the patch only rarely, but was using the Xalatan every night O.D. The patient also tolerated glasses more readily and wore them full time. Visual acuity and cover test results were stable. The family was reminded once again to continue with daily patching, to follow up with the pediatric ophthalmologist for continued monitoring of IOP under anesthesia, and to return 1 month later. Unfortunately, the patient was lost to follow-up, despite numerous attempts to contact the family. It became evident that the family had moved away.
Discussion In all types of pediatric glaucoma, the main goal of management is preservation of developing vision, not merely preservation of visual field as it is with adults. Primary congenital glaucoma has the best prognosis of all the pediatric glaucomas, with 52% to 79% of patients achieving visual acuity of 20/50 or better.6 There is no reversibility of the ocular enlargement because once the tissue has been stretched, it cannot shrink back to its original size.12 In contrast, when IOP is normalized, cupping of the optic nerve frequently can be reversed. This reversibility is possible because the optic disc tissues of an infant are not developed fully. As IOP increases, the optic nerve is compressed and moved posteriorly (because the collagenous tissues of the lamina cribrosa are not fully developed at birth), which allows the lamina to bow backward, reducing sustainable damage to the optic nerve head.13 In this case, the diagnosis was more elusive than usual, and the treatment was not standard. Before discussing this
170 case more specifically, we will review the diagnosis of more typical cases of primary congenital glaucoma.
Pathophysiology There are 2 predominant theories regarding the pathophysiology of primary congenital glaucoma. The first and most widely accepted theory is that primary congenital glaucoma is caused by “thickened beams” in the trabecular meshwork. This thickening leads to narrower trabecular spaces and reduced aqueous outflow. When such a child is born full term, the trabecular meshwork has not fully differentiated. Because of the immaturity of the trabecular meshwork at birth, there is developmental arrest of the iris, ciliary muscle, and anterior chamber angle. These structures appear as they normally would in the seventh month of gestation. Therefore, at birth, the iris, ciliary muscle, and anterior chamber angle end up in an anterior location that overlaps the trabecular meshwork, thereby also reducing aqueous outflow and preventing further differentiation of the trabecular meshwork.14-18 The second theory has as its basis a structure called Barkan’s membrane. Barkan’s membrane was thought to be an imperforate membrane that persisted after birth, covering the anterior chamber angle, thereby greatly reducing aqueous outflow. Reduced outflow would lead to increased IOP and congenital glaucoma. In recent years, this theory has been largely disproven because of the lack of histologic proof of this membrane.8,9 There has not been one truly accepted pathophysiology of congenital glaucoma.
Genetics Most commonly, primary congenital glaucoma presents in a sporadic fashion, although rarely is it hereditary. When it is hereditary, the condition is autosomal recessive with high penetrance and has been associated with abnormalities of 17 different chromosomes.6,19 Studies have located the cytochrome P4501B1 (CYP1B1) gene to be the main mutation site in congenital glaucoma, although it is unclear how this gene participates in the normal development of the eye.19
Signs and symptoms Typical anterior segment signs of primary congenital glaucoma consist of a well-established clinical triad: photophobia, blepharospasm, and epiphora. All of these clinical signs occur secondary to an increase in IOP, which stimulates corneal nerves and causes pain. Buphthalmos (ocular enlargement), corneal edema, and Haab’s striae (horizontal, diagonal, or curvilinear breaks in Descemet’s membrane) can occur as later signs if pressure is not controlled.20-22 Buphthalmos occurs because immature collagen remains distensible and leads to eye enlargement. Corneal edema and haze occur because of high pressure that compromises the endothelial hydrostatic pump mechanism.1 These signs
Optometry, Vol 78, No 4, April 2007 only occur during the first 3 years of life when the eye is still immature.8 However, Seidman et al.23 found that parents noted epiphora in only 55% of primary congenital glaucoma cases, photophobia and/or blepharospasm in 41%, corneal haze in 41%, and increased eye size in 32% of their cases. Corneal diameter should be approximately 10 mm at birth and 11 mm at 1 year of age, with an adult diameter of approximately 12 mm reached by 12 to 24 months of age.20 Posterior segment signs of primary congenital glaucoma are limited to the appearance of the optic nerve head. The increase in the size of the cup-to-disc ratio is more rapid in infants than in adults because of compression and posterior movement of tissues within the optic nerve head.13 There have been few studies measuring IOP in children without pathologic findings; therefore, no normative values have been standardized. However, it is known that IOP in the first year of life is much lower than that of an adult and that anesthesia generally lowers IOP.1 It has been proven that the normal IOP for children is at its lowest in newborns and increases with age; however, clinicians should note that any IOP from 17 to 20 mmHg is suspicious for congenital glaucoma before the age of 4 years.24 The IOP in congenital glaucoma often is considered only moderately elevated and should not be heavily relied on, as opposed to the attention given to IOP in adult glaucoma, in which it is often significantly elevated.1 When instrumentation is considered, Goldmann applanation tonometry is the “gold standard” but is difficult to obtain in many children without sedation. Hand-held tonometers are generally easier to use in children. The Perkins tonometer is considered to be the “gold standard” of portable tonometers, because Perkins is an applanation tonometer, and there have been studies illustrating the close correlation between the Goldmann tonometer and the Perkins tonometer.25 Additionally, several studies have compared Goldmann tonometry and tonometry with a Tono-pen. Tono-pen measurements with SD ⬍5% of the mean of 4 measurements correspond well to Goldmann measurements in the 11- to 20-mmHg range, reasonably well in the 21- to 30-mmHg range, and poorly over 30 mmHg. Overall, the consensus is that use of a Tono-pen is not recommended in the IOP range greater than 21 mmHg.26-28 Noncontact tonometry (NCT) can also be used on children. When reliability between NCT and Goldmann is studied, results indicate poor correlation for pressures in the 20- to 30-mmHg range but good correlation for pressures more than 30 mmHg. NCT is more useful as an IOP screening tool or when applanation tonometry is unobtainable in a child.29
Differential diagnoses When the primary congenital glaucoma triad of photophobia, epiphora, and blepharospasm, as well as any additional clinical signs, are present, it is critical to first rule out a number of other conditions. When buphthalmos is suspected, there are 2 main differentials: megalocornea and high myopia. Megalocornea is a rare, nonprogressive, gen-
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erally bilateral corneal enlargement. The corneal enlargement to 13 mm diameter or larger is present from birth. Ninety percent of cases are in males because of the X-linked recessive inheritance. Megalocornea is characterized by large, clear corneas, normal IOP, no Haab’s striae, no buphthalmos, and no pathologic optic nerve head cupping.30 Indeed, rarely, cases of simple megalocornea have been known to progress to glaucoma.31 High myopia is also accompanied by clear, normally sized corneas and normal IOP. The optic nerve head may have a normal appearance or possibly be tilted. High myopia may show other characteristic fundus signs such as scleral crescent and choroidal mottling. A cloudy cornea may be caused by birth trauma, corneal dystrophy, interstitial keratitis, metabolic disease, or anterior chamber malformation. Birth trauma, corneal dystrophy, metabolic disease, and anterior chamber malformation are apparent soon after birth. Metabolic diseases, such as Lowe’s syndrome, mucopolysaccharidosis, and cystinosis, have other systemic symptoms associated as well. Interstitial keratitis is associated with red eyes and corneal stromal blood vessels.1,8,32 When a child presents with tearing, there are 5 main conditions to rule out: congenital nasolacrimal duct obstruction, conjunctivitis, anterior uveitis, corneal abrasion/corneal foreign body, and keratoconjunctivitis sicca. Congenital nasolacrimal duct obstruction is also associated with mucopurulent discharge and matting of the eyelashes. Conjunctivitis is associated with red, inflamed eyes and possible discharge. Anterior uveitis is accompanied by photophobia, conjunctival injection, and anterior chamber cells and flare. When a corneal abrasion or foreign body is suspected, the patient is usually in pain, and corneal staining and a good history can make the definitive diagnosis. Keratoconjunctivits sicca, although uncommon in children, is a diagnosis of exclusion in cases of tearing eyes and can be determined by corneal staining, punctate corneal erosions, or reduced tear breakup time.1,32 Photophobia can be caused by corneal abrasion, foreign body, interstitial keratitis, anterior uveitis, achromatopsia, hypopigmentation syndromes (e.g., albinism), or even intermittent exotropia/high exophoria. Generally, systemic diseases are associated with cases of interstitial keratitis and anterior uveitis. Diseases such as syphilis, juvenile rheumatoid arthritis, Lyme disease, tuberculosis, and sarcoid should be considered and referral to the child’s pediatrician for a full blood workup initiated. Achromatopsia (rod monochromatism) is characterized by varying degrees of color deficiency, poor central vision, nystagmus, and pigmentary macular changes and presents bilaterally. Also presenting bilaterally, ocular albinism results in very light fundi, iris transillumination defects, and displays of visible choroidal vasculature.1,32 Blepharospasm can be caused by keratoconjunctivitis sicca, foreign body, or a neurological tic (in a patient with healthy eyes).1,32 Blepharospasm can also be related to
171 seventh cranial nerve complications or Tourette’s syndrome.32 Other common causes of primary glaucoma include such conditions as Axenfeld-Rieger syndrome, Peter’s anomaly, Sturge-Weber syndrome, neurofibromatosis, and aniridia. These diagnoses can be made on observation of the associated ocular and systemic anomalies.6
Analysis of current case In this case, the patient’s parents did not recall symptoms of tearing, photophobia, or blepharospasm. Initial examination found an enlarged right cornea, right exotropia, unilateral high myopia, a cup-to-disc ratio that was larger in the right eye than the left, and clear corneas. The bilaterally elevated intraocular pressures were considered questionable because of the patient’s inability to tolerate the examination, but the unilateral ocular enlargement warranted referral for an EUA by a pediatric ophthalmologist to rule out glaucoma. The EUA confirmed the unilateral ocular enlargement, but IOP was found to be only modestly elevated at that time. This could in part be caused by the use of a Tono-pen for measurement. Thus, the few horizontal striae noted O.D., only by initial evaluation of the ophthalmologist, were attributed to injury. This asymptomatic child was considered to have a rare case of unilateral megalocornea. The subsequent optometric examination 3 months later found newly noted, obliquely oriented striae and a higher IOP O.D., necessitating a second EUA. Because this EUA confirmed multiple new corneal striae O.D., additional corneal enlargement, and slightly elevated IOP bilaterally, the ophthalmologist rediagnosed the case as primary congenital (infantile) glaucoma and began treatment with latanoprost. Further follow-up would have allowed us to determine if his IOP responded adequately to this conservative medical management or if surgical intervention would become necessary to prevent further glaucomatous damage. There are some diagnostic limitations of the case presented. Gonioscopy was not performed by the ophthalmologist during the EUA. This omission was beyond our control. It would also have been preferable had the ophthalmologist used a more accurate method of determining IOP during the EUA. In cases of primary congenital glaucoma, gonioscopy is helpful not only to make the diagnosis of specific glaucoma type but to properly direct the patient toward definitive surgical treatment. The angle of a patient with primary congenital glaucoma may appear nearly normal with only slightly anterior iris insertion and a subtly different translucency of the trabecular meshwork. When the angle structures are still not fully differentiated, it can be challenging to label them as normal or abnormal.8 In cases in which there is markedly elevated IOP, cloudy corneas, and the classical symptomatic triad, gonioscopy is perhaps unnecessary. In this atypical situation, gonioscopy would have been extremely helpful in making the diagnosis. However,
172 based on the preponderance of evidence, this case can be diagnosed as primary congenital glaucoma. Although rare, spontaneous resolution of primary congenital glaucoma cases with no surgical treatment or minimal medical therapy has been reported by Lockie and Elder.33 Considering that not all cases of primary congenital glaucoma result in the classic symptoms, it is possible that this patient did not experience symptoms because his condition may have been less severe.23 A second EUA found new striae, elevated IOPs (for a patient of this age), and further corneal enlargement. It is possible that this patient may have had a relatively mild case of primary congenital glaucoma, affecting mainly the right eye. Although megalocornea was included in the differential, it is highly unlikely because continued corneal enlargement and new corneal striae were noted at the second EUA, which had not been seen at the first EUA. Certainly, the level of IOP in a child of this age with possible changes suggestive of infantile glaucoma clearly dictated intervention. Although very uncommon, this case clearly showed variability during the period of follow-up. Unfortunately, because this patient was lost to long-term follow-up, his future visual prognosis is uncertain. Nevertheless, the prognosis is not likely to be good without continued treatment. Of note, the presence of anisometropic amblyopia in a highly myopic eye (with anisometropia greater than 3 to 4 D), along with ipsilateral exotropia is fairly common and not necessarily attributable to glaucoma.34,35 Also noteworthy, 31% of a sample of patients with primary congenital glaucoma showed at least 2.00 D of anisometropia, and it is reported that 100% of patients have at least this degree of anisometropia if unilateral primary congenital glaucoma is diagnosed.12,50 In the presented case, we believe that glaucomatous ocular enlargement of the right eye was the underlying cause of the anisometropia that led to amblyopia and secondary exotropia. Amblyopia is common in cases of congenital glaucoma, often resulting from form deprivation (cloudy cornea), although not a factor in the current case.6 The amblyopia treatment attempted consisted of commonly used part-time, opaque, direct occlusion and eye-hand coordination activities to stimulate visual development.11 The exotropia treatment, which was limited by age, consisted of basic gross convergence exercises.
Treatment of primary congenital glaucoma Primary congenital glaucoma is better treated with surgery than medication because of the pathophysiology of the disease. Little research has been done in the area of medical management, because drugs are not often used in these cases. Generally, there are 2 indications for use of glaucoma medications in primary congenital glaucoma: before surgery, either to constrict the pupil (miotics) or to lower the IOP or as a supplement to surgery to further decrease the IOP. However, Turach et al.36 found that IOP-lowering medications adequately controlled IOP long term without surgery in approximately 10% of their cases, and Barsoum-
Optometry, Vol 78, No 4, April 2007 Homsy and Chevrette37 found control in 4% of their cases. When medical treatment is initiated, the main medications used are timolol, dorzolamide, and latanoprost.38 Timolol is a good single treatment drug when used for mild glaucoma in children but does not have the same IOP-lowering effects as a single-use drug in severe glaucoma.39,40 Reports of timolol’s usefulness when added to other medications are varied, but the overall consensus is that timolol does have additional IOP-lowering effects when used with other medications.6,39,40 It is generally not prescribed for children younger than 2 years of age because of the potential for cardiac side effects secondary to systemic absorption. Timolol has the best efficacy in patients who are at least 9 years of age.6,40 The main contraindications for pediatric timolol use include asthma, congestive heart failure, and bradycardia. The side effects are apnea, bradycardia, hypotension, increase in asthma, reduced heart rate, dissociative behavior, drowsiness, tearing, eye itching, and lightheadedness. It is rare for any of these side effects to become so severe that a patient needs to discontinue timolol therapy.39-43 One study found that use of topical timolol did reach beta blockade levels in children less than 2 years of age, but another did not find these results.21,40 Multiple studies have found that oral carbonic anhydrase inhibitors (CAIs, specifically, acetazolamide) produce more IOP reduction than topical CAIs (dorzolamide). Oral CAIs are used infrequently in children because of a much higher incidence of side effects than in adults.44 Side effects include allergy, gastrointestinal disturbance, paresthesia, and metabolic acidosis.38 Side effects reported from use of topical CAIs include taste perversion, headaches, upper respiratory tract infections, ocular burning/stinging, and ocular hyperemia.45 Topical CAIs are an effective first- or second-line medical treatment. The IOP reduction rate of topical dorzolamide has been reported to vary from 14% to 36%.44,46 Latanoprost is systemically safer than timolol and dorzolamide but has a greater nonresponse rate. Latanoprost causes only rare side effects, including conjunctival redness and irritation. This medication is not as effective in children as it is in adults and has its best IOP-reducing effects on juvenile open-angle glaucoma.47 Adrenergic agonists are rarely used because of severe potential side effects, most notably effects on the central nervous system causing severe fatigue and drowsiness. It is unclear why the ophthalmologist treating this patient chose latanoprost over surgery or the first-line medical treatment (timolol) for a case diagnosed as primary congenital glaucoma. Many surgical options exist for treatment of primary congenital glaucoma. The procedures performed with the best success on children are different than those for adults because of the differences in pathophysiology of the disease in adults and children.1,6,48 Overall, the best success rate with surgery occurs when done by the age of 3 years. Goniotomy and trabeculotomy are the procedures most commonly performed on children and have the best success
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rates.37,48 Both of these procedures restore physiologic outflow from the anterior chamber angle.1 Goniotomy involves using a needle, knife, or laser to make an incision into the anterior aspect of the middle third of the trabecular meshwork over 360°.48,49 The success rate is 70% to 90%, if done in the first 2 years of life, and success can generally be determined within a 6-month postoperative period.50 As a child becomes older than 2 years, the trabecular meshwork becomes more collagenous, and this procedure becomes less useful.51 The success of goniotomy is not limited by duration of the disease or level of intraocular pressure before treatment.50 The main limitation to this procedure is corneal clarity. When the cornea is cloudy, this procedure cannot be performed without an endoscope to better visualize the angle. Also noteworthy, if the cornea is clear, the success rate is the same, independent of corneal size.6,12,49,50,52 The main complications of goniotomy include self-limited hyphema, iridodialysis, cyclodialysis, and localized Descemet’s detachment.9 About 25% of patients who have undergone goniotomy require retreatment.50,53 Trabeculotomy involves an external dissection of Schlemm’s canal, with a metal probe inserted and rotated into the anterior chamber inferotemporally. Between 100° and 360° of the angle are treated; this decision is entirely dependent on the surgeon and his or her comfort and experience with the procedure.48,51 Trabeculotomy creates a direct continuity between Schlemm’s canal and the anterior chamber. Complications are similar to goniotomy. Trabeculotomy can be performed with a cloudy cornea because there is less need to visualize the angle than with goniotomy. Success rates for trabeculotomy have been reported by some sources to be better than for goniotomy, but generally it is accepted that the success rates are equal.54,55 If goniotomy or trabeculotomy fails the first time, a patient can be retreated a second time with a good success rate. If after this second treatment the glaucoma is still uncontrolled, then other procedures are generally performed.37 Uncontrolled glaucomatous optic nerve damage and amblyopia are the main reasons for postsurgical poor vision.6 Filtration or trabeculectomy is a second-line procedure if goniotomy or trabeculotomy fails.56,57 However, trabeculectomy becomes the first choice for treatment if the patient is older than 3 years because of the aforementioned physiologic changes that the eye goes through around the 2- to 3-year mark.8,48,58 Trabeculectomy is more often used outside the United States at any age because the surgeons have limited goniotomy/trabeculotomy experience. Trabeculectomy can be performed despite a cloudy cornea.58,59 There is more failure with trabeculectomy than goniotomy or trabeculotomy because of complications (including scarring over the bleb). Therefore, adjunctive therapy is generally used in the form of antifibrotic agents like mitomycin C, 5-fluoruracil, or betairradiation. Mitomycin C produces more ocular side effects than the milder 5-fluorouracil and beta-irradiation.1,58 Varying reports exist of use of these antifibrotic agents and success rates
173 (IOP control) with and without these products.6,49,58,59 The general consensus among surgeons is to incorporate antifibrotics; doing so yields an average 60% success rate for filtration surgery. When these agents are not incorporated, the success rate is drastically lower at 30% to 35%. Regardless of whether adjunctive antifibrotic agents are used, there are more complications with trabeculectomy than with goniotomy or trabeculotomy, most important bleb-related endophthalmitis.6,59 Other surgical procedures for treatment of infantile glaucoma include a combined trabeculotomy–trabeculectomy, aqueous shunting, and cyclodestruction. The combined trabeculotomy–trabeculectomy procedure has varying results. There is potential for more complications with the combined procedure than with a single procedure.6,51,60 The most common aqueous shunt device is the Molteno valve. Aqueous shunting also requires adjunctive therapy, like trabeculectomy, to decrease fibrosis and tissue adhesions around the implant area. Aqueous shunting has many complications, most of which relate to the implant, and is only used if other surgical procedures fail.6,56 Cyclodestruction is the procedure of last resort, reserved for children with a poor visual prognosis or those who have had multiple failed surgeries. It is unpopular because of the low success rate and frequent need for retreatment. Cyclodestruction also has a high rate of complications, which are more severe than those of the other surgical procedures.1,6,48,61
Conclusion Primary congenital glaucoma is a sight-threatening disease. This condition commonly presents with a clinical triad of photophobia, epiphora, and blepharospasm. It is important that eye care providers be aware of the clinical signs. The presence of a unilateral or bilateral enlarged cornea is another indication to investigate for glaucoma in a child, even without the classic signs. Management may include medical, surgical, optical, and amblyopia treatment. Medical treatment is rarely initiated because of the poor response rate of primary congenital glaucoma. Surgical treatment is the best option because of the pathophysiology of the disease, with either goniotomy or trabeculotomy as the first choice. Amblyopia is a common secondary condition, which, if untreated, may be sight threatening as well. Appropriate optical correction and protective eyewear are important for optimal visual function. The combined efforts of ophthalmic professionals are required to attain the best visual acuity for these patients. Primary congenital glaucoma has a good visual outcome in many cases when there is adequate IOP control and appropriate management of accompanying conditions.
Acknowledgments The authors thank Sandra Block, O.D., M.Ed., Christine Allison, O.D., and Michelle Chan, O.D., for their helpful
174 comments on earlier versions of this manuscript. This case was presented as a poster at the 2004 Annual Meeting of the American Academy of Optometry in Tampa, Florida.
References 1. Rubin S, Marcus C. Glaucoma in childhood. Pediatric Ophthalmology, The Ophthalmology Clinics of North America 1996;9:215-6. 2. Genick A. Epidemiology and genetics of primary congenital glaucoma in Slovakia: Description of a form of primary congenital glaucoma in gypsies with autosomal recessive inheritance and complete penetrance. Dev Ophthalmol 1989;16:75-115. 3. Francois J. Heredity in ophthalmology. St. Louis: Mosby; 1961:218-25. 4. Francois J. Congenital glaucoma and its inheritance. Ophthalmologica 1972;181:61-73. 5. Basic and clinical science course, section 10, glaucoma 1993-1994. San Francisco: American Academy of Ophthalmology, 1993. 6. Beck A. Diagnosis and management of pediatric glaucoma. Pediatric Ophthalmology, The Ophthalmology Clinics of North America 2001; 14:501-12. 7. Kanski JJ. Clinical ophthalmology, 4th ed. Boston: ButterworthHeinemann, 1999;143, 235-8. 8. DeLuise VP, Anderson DR. Primary infantile glaucoma (congenital glaucoma). Surv Ophthalmol 1983;28:1-19. 9. Barkan O. Technic of goniotomy. Arch Ophthalmol 1938;19:217-23. 10. Frantz KA, Peters RJ, Maino DM, et al. Effect of resisting tonometry on intraocular pressure. J Am Optom Assoc 1994;65:732-6. 11. Caloroso EE, Rouse MW. Clinical management of strabismus. Boston: Butterworth-Heinemann, 1993. 12. Robin AL, Quigley HA, Pollack IP, et al. An analysis of visual acuity, visual fields, and disk cupping in childhood glaucoma. Am J Ophthalmol 1979;88:847-58. 13. Quigley HA. The pathogenesis of reversible cupping in congenital glaucoma. Am J Ophthalmol 1977;84:358-70. 14. Anderson DR. The development of the trabecular meshwork and its abnormality in primary infantile glaucoma. Trans Am Ophthalmol Soc 1981;79:458-85. 15. Trachimowicz R. Review of embryology and its relation to ocular disease and the pediatric population. Optom Vis Sci 1994;71:154-63. 16. Tawara A, Inomata H. Congenital abnormalities of the trabecular meshwork in primary glaucoma with open angle. Glaucoma 1987;9: 28-34. 17. Arora R, Aggarwal HC, Sood NN. Observations on the histopathology of trabecular meshwork with reference to the pathogenesis of congenital glaucoma. Glaucoma 1990;12:112-6. 18. Maumenee AE. Further observations on the pathogenesis of congenital glaucoma. Am J Ophthalmol 1963;55:1163-76. 19. Safarazi M, Stoilov I. Molecular genetics of primary congenital glaucoma. Eye 2000;14:422-8. 20. Isenberg S. The eye in infancy, 2nd ed. St. Louis: Mosby; 1993:64, 301. 21. Hoskins HD, Kass M. Becker-Shaffer’s diagnosis and therapy of the glaucomas, 6th ed. St. Louis: CV Mosby, 1989;364-5. 22. Chandler PA, Grant WM. Lectures on glaucoma. Philadelphia: Lea & Febiger, 1965;312-3. 23. Seidman DJ, Nelson LB, Calhoun JH, et al. Signs and symptoms in presentation of primary infantile glaucoma. Pediatrics 1986;77:399-404. 24. Pensiero S, Da Pozzo S, Perissutti P, et al. Normal intraocular pressure in children. J Pediatr Ophthalmol Strabismus 1992;29:79-84. 25. Garcia-Resua C, Gonzalez-Meijome JM, Gilino J, et al. Accuracy of the new ICare rebound tonometer vs. other portable tonometers in healthy eyes. Optom Vis Sci 2006;83:102-7. 26. Wingert TA, Bassi CJ, McAlister WH, et al. Clinical evaluation of five portable tonometers. J Am Optom Assoc 1995;66:670-4. 27. Armstrong TA. Evaluation of the Tono-Pen and the Pulsair tonometers. Am J Ophthalmol 1990;109:716-20.
Optometry, Vol 78, No 4, April 2007 28. Frenkel REP, Hong YJ, Shin DH. Comparison of the Tono-Pen to the Goldmann applanation tonometer. Arch Ophthalmol 1988;106:750-3. 29. Lagerlöf O. Airpuff tonometry versus applanation tonometry. Acta Ophthalmol 1990;68:221-4. 30. Oetting TA, Hendrix MA. Megalocornea (emedicine database). Available at: http://www.emedicine.com/oph/topic549.htm. Last accessed June 18, 2006. 31. Kluyskens J. Le glaucome congenital. Bull Soc Belg Ophthalmol 1950;94:10,194-5. 32. Rhee D, Ryfer M. The Wills eye manual, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 1999. 33. Lockie P, Elder J. Spontaneous resolution of primary congenital glaucoma. Aust NZ J Ophthalmol 1989;17:75-7. 34. Tanlamai T, Goss DA. Prevalence of monocular amblyopia among anisometropic amblyopes. Am J Optom Physiol Opt 1979;56:704-15. 35. Rouse MW, Cooper JS, Cotter SA, et al. Optometric clinical practice guideline: care of the patient with amblyopia. St. Louis: American Optometric Association, 1994;5-7. 36. Turach ME, Gülderen A, Aysun I. Medical and surgical aspects of congenital glaucoma. Acta Ophthalmol Scand 1995;73:261-3. 37. Barsoum-Homsy M, Chevrette L. Incidence and prognosis of childhood glaucoma: A study of 63 cases. Ophthalmology 1986;93:1323-7. 38. Talbot AWR, Russell-Eggit I. Pharmaceutical management of the childhood glaucomas. Exp Opin Pharmacother 2000;1:697-711. 39. Boger W, Walton D. Timolol in uncontrolled childhood glaucomas. Ophthalmology 1981;88:253-8. 40. McMahon C, Hetherington J, Hoskins H, et al. Timolol and the pediatric glaucomas. Ophthalmology 1981;88:249-52. 41. Zimmerman T, Kooner K, Morgan K. Safety and efficacy of timolol in pediatric glaucoma. Surv Ophthalmol 1983;28:262-4. 42. Hoskins H, Hetherington J, Magee S, et al. Clinical experience with timolol in childhood glaucoma. Arch Ophthalmol 1985;103:1163-5. 43. Olson RJ, Bromberg BB, Zimmerman TJ. Apneic spells associated with timolol therapy in a neonate. Am J Ophthalmol 1979;88:120-2. 44. Protellos M, Buckley EG, Freedman SF. Topical versus oral carbonic anhydrase inhibitor therapy for pediatric glaucoma. J AAPOS 1998; 2:43-7. 45. Ott EZ, Mills MD, Arango S, et al. A randomized trial assessing dorzolamide in patients with glaucoma who are younger than 6 years. Arch Ophthalmol 2005;123:1177-86. 46. Enyedi LB, Freedman SF. Safety and efficacy of brimonidine in children with glaucoma. J AAPOS 2001;5:281-4. 47. Enyedi L, Freedman S, Buckley E. The effectiveness of latanoprost for the treatment of pediatric glaucoma. J AAPOS 1999;3:33-9. 48. Wilson R. Changes in surgical care of pediatric glaucoma. Rev Ophthalmol 2002;9(2):82-5. 49. Sun W, Shen J, Shetlar D, et al. Endoscopic goniotomy with the free electron laser in congenital glaucoma rabbits. J Glaucoma 2000;9: 325-33. 50. Broughton WL, Parks MM. An analysis of treatment of congenital glaucoma by goniotomy. Am J Ophthalmol 1981;91:566-72. 51. Mandal A, Naduvilath T, Jayagandan A. Surgical results of combined trabeculotomy-trabeculectomy for developmental glaucoma. Ophthalmology 1998:105:974-82. 52. Joos KM, Alward WLM, Folberg R. Experimental endoscopic goniotomy: A potential treatment for primary infantile glaucoma. Ophthalmology 1993;100:1066-70. 53. Russell-Eggitt IM, Rice NSC, Jay B, et al. Relapse following goniotomy for congenital glaucoma due to trabecular dysgenesis. Eye 1992;6:197-200. 54. Akimoto M, Tanihara H, Negi A, et al. Surgical results of trabeculotomy ab externo for developmental glaucoma. Arch Ophthalmol 1994;112:1540-4. 55. McPherson SD, McFarland D. External trabeculotomy for developmental glaucoma. Ophthalmology 1980;87:302-5. 56. Pereira M, Araujo S, Wilson R, et al. Aqueous shunts for intractable glaucoma in infants. Ophthal Surg Lasers 2002;33:19-29.
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Clinical Care
57. Gressel MG, Heuer DK, Parrish II RK. Trabeculectomy in young patients. Ophthalmology 1984;91:1242-6. 58. Khaw P. What is the best primary surgical treatment for the infantile glaucomas? Br J Ophthalmol 1996;80:495-6. 59. Dureau P, Dollfus H, Cassegrain C, et al. Long-term results of trabeculectomy for congenital glaucoma. J Pediatr Ophthalmol Strabismus 1998;35:198-202.
175 60. Mandal A, Bhatia P, Gothwal V, et al. Safety and efficacy of simultaneous bilateral primary combined trabeculotomy-trabeculectomy for developmental glaucoma. Indian J Ophthalmol 2002; 50:13-9. 61. Al Faran MF, Tomey KF, Al Mutlaq FA. Cyclocryotherapy in selected cases of congenital glaucoma. Ophthal Surg 1990;21:794-8.