- Email: [email protected]
Retinitis pigmentosa, nanophthalmos, and optic disc drusen
Retinitis Pigmentosa, Nanophthalmos, and Optic Disc Drusen A Case Report Yvonne M. Buys, MD, FRCS(C),1 Charles J. Pavlin, MD, FRCS(C)1,2 Objective: Although the associations of retinitis pigmentosa (RP) with nanophthalmos/microphthalmos and RP with optic disc drusen have previously been recognized, the concurrence of all three features, as far as the authors are aware, has not previously been reported. Design: Case report. Results: The authors report a sporadic case of nanophthalmos, RP, and optic nerve drusen with the additional complication of chronic angle closure glaucoma. Conclusions: Visual loss may be secondary to the complications of nanophthalmos, RP, or optic nerve drusen. Chronic angle closure may be caused by choroidal effusion with serous retinal detachment, which may, in turn, cause a pseudo-RP picture. It is therefore important to recognize the possible association of true RP with nanophthalmos as a cause for visual deterioration. Ophthalmology 1999;106:619 – 622 Although the associations of retinitis pigmentosa (RP) with nanophthalmos/microphthalmos1–3 and RP with optic nerve drusen4 have previously been recognized, the concurrence of all three features, as far as we are aware, has not previously been reported. Because visual loss may be secondary to the complications of nanophthalmos, RP, or optic nerve drusen, the recognition of these associations is essential for clinical management and patient counseling. We report a sporadic case of nanophthalmos, RP, and optic nerve drusen with the additional complication of chronic angle closure glaucoma. Chronic angle closure may sometimes be caused by choroidal effusion with serous retinal detachment, which may, in turn, cause a pseudo-RP picture. It is therefore important to recognize the possible association of true RP with nanophthalmos.
Case Report A 68-year-old man was diagnosed with RP in 1977. He has had an extinguished electroretinogram (ERG) and progressive visual field loss since the time of diagnosis. The ERG was performed in accordance with International Society for the Clinical Electrophysiology of Vision standards.5 He presented with central visual fields of less than 10°. Three years prior, he was diagnosed with glau-
Originally received: March 13, 1998. Revision accepted: October 19, 1998. Manuscript no. 98134. 1 Department of Ophthalmology, The Toronto Hospital, Toronto, Ontario, Canada. 2 Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada. Address correspondence to Yvonne M. Buys, MD, FRCS(C), The Toronto Hospital, Western Division, Edith Cavell Wing 7-042, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.
coma, which had been managed medically. At the time of presentation, he was using pilocarpine 1% three times daily in both eyes. His medical history was significant for a myocardial infarction 6 months earlier, for which he was taking diltiazem and acetylsalicylic acid. His family history was negative for any ocular disease. On examination, his best-corrected visual acuity was 20/400 in the right eye with ⫹10.50 diopters and 20/80 in the left eye with ⫹12.25 diopters. He had a right esotropia. Anterior segment examination revealed corneal diameters of 9 mm bilaterally, mild nuclear sclerosis, and shallow anterior chambers. On gonioscopy, the angles were closed for 270° and slitlike for the inferior 90°. There were broad peripheral anterior synechiae in the inferior temporal and nasal quadrant in each eye. Posterior synechiae were also present bilaterally. The intraocular pressure by applanation tonometry was 14 millimeters of mercury (mmHg) in the right eye and 13 mmHg in the left eye. Because the angles were narrow and peripheral anterior synechiae had formed bilaterally, neodymium:YAG (Nd:YAG) laser iridotomies were performed without consequence. Pilocarpine was discontinued, and the intraocular pressure, by applanation tonometry, after 2 weeks with no medication remained stable at 16 mmHg in the right eye and 12 mmHg in the left eye. After confirming bilateral patent iridotomies, a dilated funduscopic examination was performed. The pupils were difficult to dilate because of posterior synechiae precluding examination beyond the midperiphery or fundus photography. Fundus examination revealed marked bilateral changes of a retinal dystrophy including “bone spicule” pigmentary changes in the posterior pole with some perivascular concentration of hyperpigmentation along with blunting of the macular reflex and wrinkling of the internallimiting membrane but no vascular attenuation. There was marked optic nerve head drusen and no cupping. A B-scan (Cooper Vision, Sacramento, CA) confirmed optic nerve head drusen (Fig 1). Axial lengths measured by A-scan ultrasonography were 16.10 mm for the right eye and 15.86 mm for the left eye. An ultrasound biomicroscopy (Zeiss-Humphrey, San Leandro, CA) was obtained that confirmed narrow angles and showed the iris arising from the anterior aspect of the ciliary
619
Ophthalmology Volume 106, Number 3, March 1999
Figure 1. A, A-scan ultrasound showing short axial length and large lens. B, B-scan ultrasound showing optic nerve head drusen (arrow).
processes, producing a plateau-like configuration (Fig 2). The anterior sclera was of normal thickness. Figure 3 demonstrates the pedigree of this case. The proband’s 33-year-old son was also examined and found to have an entirely normal eye examination with no evidence of a retinal dystrophy. He had grade 3 to 4 angles bilaterally with only two tiny inferior peripheral anterior synechiae in each eye. Coincidentally, he had a suspicious elevated pigmented lesion, which is currently being evaluated.
Discussion Microphthalmia may present as an isolated ocular anomaly, in association with other ocular abnormalities (most commonly coloboma or cataract) and/or in combination with
Figure 2. Ultrasound biomicroscopic image showing narrow angle (arrow), iris arising from relatively anterior aspect of ciliary process producing plateaulike configuration, and anterior sclera of normal thickness (arrowhead).
620
systemic abnormalities (e.g., lateral facial dysplasia). Microphthalmia and microcornea may be seen separately or concurrently. We are not aware of evidence suggesting that either anomaly in isolation, except perhaps at the extreme ends of the spectrum, is associated with closed-angle glaucoma. Nanophthalmos is a specific type of microphthalmia that has been characterized variably as an eye with an axial length of less than 13 to 18.5 mm associated with a relatively large lens to globe volume ratio, shallow anterior chamber, tendency toward uveal effusion (spontaneous or postoperative), and, in particular, thick sclera.3,6 –10 The association with narrow/closed-angle glaucoma is well recognized.2,3,6,7,9 Although our patient did not demonstrate thickened sclera by ultrasound biomicroscopy, other features of nanophthalmos were seen. Histologic confirmation of sclera abnormalities, not available in our patient, may be more important as a diagnostic criterion than ultrasound biomicroscopy.8,10 The association of nanophthalmos with tapetoretinal degeneration with and without glaucoma has previously been described. In 1958, Hermann1 reported a four-generation
Figure 3. Pedigree. / indicates deceased individuals; ⫹ indicates examined individuals.
Buys and Pavlin 䡠 RP, Nanophthalmos, and Disc Drusen pedigree (Mendelian Inheritance in Man—MIM #157100) with male-to-male transmission indicating autosomal dominance. Although axial length measurements, ERG, and gonioscopy were not available, this early report suggests an entity similar to that seen in our case. Hermann cites a previous study in the German literature by Catsch in which there were two reported cases of microphthalmia with RP, which, in this population study, represented 3% of all RP cases. Hermann’s patients showed a variety of fundus pigmentary abnormalities with or without the typical bone spicule pigmentary changes commonly associated with RP and seen in our case. However, many of these patients had moderate myopia, unlike our patient. In 1965, Franceschetti and Gernet2 reported a presumed autosomal-recessive pedigree (MIM #251700) of microphthalmia without microcornea associated with macrophakia, high hyperopia, a retinal dystrophy, and narrow angle glaucoma. Unlike our patient, these individuals also had dental anomalies and a fundus more reminiscent of fundus flavimaculatus or fundus albipunctatus. In addition, the ERG was variably affected, dark adaptation was normal, and cystoid macular edema may have been present. The consanguineous family reported by MacKay and coworkers,7 demonstrating pseudodominant autosomal-recessive inheritance, also had a cystic macular degeneration that showed no leakage on fluorescein angiography. With age, the cysts resolved, leaving a pigmentary maculopathy. Although these patients also showed narrow/closed-angle glaucoma, microphthalmia, and a pigmentary midperipheral retinopathy similar to those seen in our patient, vitreous abnormalities and normal corneal diameters were seen. In their pedigree consistent with autosomal-recessive inheritance, patients with nanophthalmia, as discussed by Cross and Yoder,6 were also found to have abnormalities of the retinal pigment epithelium and choroid by angiography, which were described on clinical examination as “mottling” of the retinal pigmentation. Perhaps the case report that provides the closest correlation to our patient is the sporadic case of Ghose and coworkers.3 Their 56-year-old male had closed-angle glaucoma, nanophthalmos, microcornea, and a similar retinal appearance. Unfortunately, ERG data are incomplete other than to state that the responses were subnormal through an undilated pupil. No mention is made of the presence of optic nerve drusen, although the nerve is called “hypermetropic” with “mild pallor” and “normal cup– disc ratios.” Optic disc drusen occur in 0.34% of individuals and may be inherited in an autosomal-dominant fashion with variable penetrance or autosomal recessive.4 Optic discs containing drusen are often described as small and crowded, lacking a physiologic cup. This anatomic arrangement may well predispose to the formation of optic disc drusen, which are thought to be the result of a disturbance of axoplasmic transport at the lamina cribrosa, resulting in the extrusion of mitochondria filled with calcium crystals.11 Interestingly, optic disc drusen have been reported to occur in association with hypermetropia.12 Considering the pathogenesis of optic disc drusen, the nanophthalmic eye with its short axial length and thickened sclera seems predisposed to this condition.
To our knowledge, this is the first report of the association of nanophthalmos and optic disc drusen. Optic disc drusen have also been reported to occur in association with RP4,13,14 and angioid streaks.15 In a review of 262 patients with RP, the frequency of optic nerve or parapapillary drusen was 9.2%.13 Edwards et al14 reported the frequency in Usher syndrome to be 8% to 35%. In an exhaustive review of the 41 cases of RP with optic nerve drusen reported up to 1966 by Lorentzen,4 none were found to have nanophthalmos or microphthalmos. The cause of nanophthalmos has been debated. Studies have suggested an abnormality of collagen fibril formation, fibronectin production, or other primary abnormalities related to collagen production and aggregation, which may have secondary effects on, or be related to, primary defects of proteoglycan and/or glycosaminoglycan production and metabolism.8,10 Other disorders of collagen production, such as Stickler syndrome, may also be associated with a retinal dystrophy. The relationship between collagen disorders and retinal degeneration is not well understood, but may be operant here. We are not aware of any genetic linkage data to suggest a possible locus for nanophthalmos that might allow us to consider the possibility of a contiguous gene syndrome as the cause of concurrence. Similar scleral collagen abnormalities have been reported in Hallerman–Streiff syndrome,10 but to our knowledge no patient with this congenital disorder has also had a tapetoretinal degeneration. Hallerman–Streiff syndrome is associated with microphthalmia and glaucoma, but our patient had neither the other craniofacial stigmata nor cataract.16 One must also consider the possibility of the presence of a prior uveal effusion causing a secondary pseudo-RP after retinal detachment with apoptosis, a mechanism of photoreceptor cell death seen in both RP and retinal detachment.17 Uveal effusion and nonrhegmatogenous retinal detachment may occur spontaneously or as a complication of ocular surgery in nanophthalmos.18 The currently accepted mechanism of uveal effusion is that venous drainage is impaired because of the abnormal sclera.19,20 Our patient also demonstrated unusual scalloped peripheral iridocorneal adhesions. These have previously been noted in cases reported by MacKay et al.7 This finding may be due to a prior episode of complete angle closure secondary to peripheral uveal effusion with rotation of the ciliary body anteriorly. Yet one might not expect an extinguished ERG with a history of progressive visual loss if a uveal effusion with detachment were the cause. Nanophthalmos may also be associated with visual field and acuity loss secondary to either glaucoma or uveal effusions. Optic disc drusen not infrequently result in visual field loss21,22 and less commonly in visual acuity loss.21 Finally, in sporadic cases such as ours, one might consider causes due to nongenetic intrauterine processes. For example, congenital rubella infection is known to be associated with glaucoma, a retinal pigmentary disorder, and microphthalmia. Our patient showed no other stigmata of congenital rubella such as hearing loss, congenital cardiac disease, or congenital cataract. Our patient has posterior synechiae and anterior synechiae, both of which may have been caused by intraocular inflamma-
621
Ophthalmology Volume 106, Number 3, March 1999 tion. It is interesting that Sjo¨gren and Larsson reported microphthalmia with tapetoretinal degeneration in a child with scoliosis and another with associated spastic diplegia.23 Both children had renal disease and both were thought to have possibly been affected as a result of a viral embryopathy. We believe that our patient represents a specific syndrome of nanophthalmos associated with RP and optic nerve drusen. Retinitis pigmentosa is the most likely cause of the decreased visual acuity and field. Our case illustrates the need to consider tapetoretinal degeneration as the cause of visual loss in the patient with nanophthalmia.
References 1. Hermann P. Le syndrome microphtalmie-re´tinite pigmentaireglaucome. Arch Ophthalmol (Paris) 1958;18:17–24. 2. Franceschetti A, Gernet H. Diagnostic ultrasonique d’une microphtalmie sans microcorne´e, avec macrophakie, haute hyperme´tropie associe´e a` une de´ge´nerescence tape´to-re´tinienee, une disposition glaucomateuse et des anomalies dentaires. Arch Ophthalmol (Paris) 1965;25:105–16. 3. Ghose S, Sachdev MS, Kumar H. Bilateral nanophthalmos, pigmentary retinal dystrophy, and angle closure glaucoma—a new syndrome? Br J Ophthalmol 1985;69:624 – 8. 4. Lorentzen SE. Drusen of the optic disk. A clinical and genetic study. Acta Ophthalmol Suppl 1966;90:1–79. 5. Standard for clinical electroretinography. International Standardization Committee. Arch Ophthalmol 1989;107:816 –9. 6. Cross HE, Yoder F. Familial nanophthalmos. Am J Ophthalmol 1976;81:300 – 6. 7. MacKay CJ, Shek MS, Carr RE, et al. Retinal degeneration with nanophthalmos, cystic macular degeneration, and angle closure glaucoma. A new recessive syndrome. Arch Ophthalmol 1987;105:366 –71. 8. Yue BYJT, Kurosawa A, Duvall J, et al. Nanophthalmic sclera. Fibronectin studies. Ophthalmology 1988;95:56 – 60. 9. Good WV, Stern WH. Recurrent nanophthalmic uveal effusion syndrome following laser trabeculoplasty. Am J Ophthalmol 1988;106:234 –5.
622
10. Stewart DH III, Streeten BW, Brockhurst RJ, et al. Abnormal scleral collagen in nanophthalmous: an ultrastructural study. Arch Ophthalmol 1991;109:1017–25. 11. Tso MOM. Pathology and pathogenesis of drusen of the optic nervehead. Ophthalmology 1981;88:1066 – 80. 12. Strassman I, Silverston B, Seelenfreund M, et al. Optic disc drusen and hypermetropia. Metab Pediatr System Ophthalmol 1991;14:37–9. 13. Grover S, Fishman GA, Brown J Jr. Frequency of optic disc or parapapillary nerve fiber layer drusen in retinitis pigmentosa. Ophthalmology 1997;104:295– 8. 14. Edwards A, Grover S, Fishman GA. Frequency of photographically apparent optic disc and parapapillary nerve fiber layer drusen in Usher syndrome. Retina 1996;16:388 –92. 15. Coleman K, Ross MH, Mc Cabe M, et al. Disk drusen and angioid streaks in pseudoxanthoma elasticum. Am J Ophthalmol 1991;112:166 –70. 16. Cohen MM Jr. Hallermann–Streiff syndrome: a review. Am J Med Genet 1991;41:488 –99. 17. Chang CJ, Lai WW, Edward DP, Tso MOM. Apoptotic photoreceptor cell death after traumatic retinal detachment in humans. Arch Ophthalmol 1995;113:880 – 6. 18. Ryan EA, Zwaan J, Chylack LT Jr. Nanophthalmos with uveal effusion. Clinical and embryologic considerations. Ophthalmology 1982;89:1013–7. 19. Shaffer RN. Discussion. Trans Am Ophthalmol Soc 1975;73: 119 –20. Comment on: Trans Am Ophthalmol Soc 1975;73: 97–118. 20. Singh OS, Simmons RJ, Brockhurst RJ, Trempe CL. Nanophthalmos: a perspective on identification and therapy. Ophthalmology 1982;89:1006 –12. 21. Scholl GB, Song HS, Winkler DE, Wray SH. The pattern visual evoked potential and pattern electroretinogram in drusen-associated optic neuropathy. Arch Ophthalmol 1992;110: 75– 81. 22. Moody TA, Irvine AR, Cahn PH, et al. Sudden visual field constriction associated with optic disc drusen. J Clin Neuroophthalmol 1993;13:8 –13. 23. Sjo¨gren T, Larsson T. Microphthalmos and anophthalmos with or without coincident oligophrenia; a clinical and genetic-statistical study. Acta Psychiatr Neurol Suppl 1949;56:1– 103.
Case Report A 68-year-old man was diagnosed with RP in 1977. He has had an extinguished electroretinogram (ERG) and progressive visual field loss since the time of diagnosis. The ERG was performed in accordance with International Society for the Clinical Electrophysiology of Vision standards.5 He presented with central visual fields of less than 10°. Three years prior, he was diagnosed with glau-
Originally received: March 13, 1998. Revision accepted: October 19, 1998. Manuscript no. 98134. 1 Department of Ophthalmology, The Toronto Hospital, Toronto, Ontario, Canada. 2 Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada. Address correspondence to Yvonne M. Buys, MD, FRCS(C), The Toronto Hospital, Western Division, Edith Cavell Wing 7-042, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.
coma, which had been managed medically. At the time of presentation, he was using pilocarpine 1% three times daily in both eyes. His medical history was significant for a myocardial infarction 6 months earlier, for which he was taking diltiazem and acetylsalicylic acid. His family history was negative for any ocular disease. On examination, his best-corrected visual acuity was 20/400 in the right eye with ⫹10.50 diopters and 20/80 in the left eye with ⫹12.25 diopters. He had a right esotropia. Anterior segment examination revealed corneal diameters of 9 mm bilaterally, mild nuclear sclerosis, and shallow anterior chambers. On gonioscopy, the angles were closed for 270° and slitlike for the inferior 90°. There were broad peripheral anterior synechiae in the inferior temporal and nasal quadrant in each eye. Posterior synechiae were also present bilaterally. The intraocular pressure by applanation tonometry was 14 millimeters of mercury (mmHg) in the right eye and 13 mmHg in the left eye. Because the angles were narrow and peripheral anterior synechiae had formed bilaterally, neodymium:YAG (Nd:YAG) laser iridotomies were performed without consequence. Pilocarpine was discontinued, and the intraocular pressure, by applanation tonometry, after 2 weeks with no medication remained stable at 16 mmHg in the right eye and 12 mmHg in the left eye. After confirming bilateral patent iridotomies, a dilated funduscopic examination was performed. The pupils were difficult to dilate because of posterior synechiae precluding examination beyond the midperiphery or fundus photography. Fundus examination revealed marked bilateral changes of a retinal dystrophy including “bone spicule” pigmentary changes in the posterior pole with some perivascular concentration of hyperpigmentation along with blunting of the macular reflex and wrinkling of the internallimiting membrane but no vascular attenuation. There was marked optic nerve head drusen and no cupping. A B-scan (Cooper Vision, Sacramento, CA) confirmed optic nerve head drusen (Fig 1). Axial lengths measured by A-scan ultrasonography were 16.10 mm for the right eye and 15.86 mm for the left eye. An ultrasound biomicroscopy (Zeiss-Humphrey, San Leandro, CA) was obtained that confirmed narrow angles and showed the iris arising from the anterior aspect of the ciliary
619
Ophthalmology Volume 106, Number 3, March 1999
Figure 1. A, A-scan ultrasound showing short axial length and large lens. B, B-scan ultrasound showing optic nerve head drusen (arrow).
processes, producing a plateau-like configuration (Fig 2). The anterior sclera was of normal thickness. Figure 3 demonstrates the pedigree of this case. The proband’s 33-year-old son was also examined and found to have an entirely normal eye examination with no evidence of a retinal dystrophy. He had grade 3 to 4 angles bilaterally with only two tiny inferior peripheral anterior synechiae in each eye. Coincidentally, he had a suspicious elevated pigmented lesion, which is currently being evaluated.
Discussion Microphthalmia may present as an isolated ocular anomaly, in association with other ocular abnormalities (most commonly coloboma or cataract) and/or in combination with
Figure 2. Ultrasound biomicroscopic image showing narrow angle (arrow), iris arising from relatively anterior aspect of ciliary process producing plateaulike configuration, and anterior sclera of normal thickness (arrowhead).
620
systemic abnormalities (e.g., lateral facial dysplasia). Microphthalmia and microcornea may be seen separately or concurrently. We are not aware of evidence suggesting that either anomaly in isolation, except perhaps at the extreme ends of the spectrum, is associated with closed-angle glaucoma. Nanophthalmos is a specific type of microphthalmia that has been characterized variably as an eye with an axial length of less than 13 to 18.5 mm associated with a relatively large lens to globe volume ratio, shallow anterior chamber, tendency toward uveal effusion (spontaneous or postoperative), and, in particular, thick sclera.3,6 –10 The association with narrow/closed-angle glaucoma is well recognized.2,3,6,7,9 Although our patient did not demonstrate thickened sclera by ultrasound biomicroscopy, other features of nanophthalmos were seen. Histologic confirmation of sclera abnormalities, not available in our patient, may be more important as a diagnostic criterion than ultrasound biomicroscopy.8,10 The association of nanophthalmos with tapetoretinal degeneration with and without glaucoma has previously been described. In 1958, Hermann1 reported a four-generation
Figure 3. Pedigree. / indicates deceased individuals; ⫹ indicates examined individuals.
Buys and Pavlin 䡠 RP, Nanophthalmos, and Disc Drusen pedigree (Mendelian Inheritance in Man—MIM #157100) with male-to-male transmission indicating autosomal dominance. Although axial length measurements, ERG, and gonioscopy were not available, this early report suggests an entity similar to that seen in our case. Hermann cites a previous study in the German literature by Catsch in which there were two reported cases of microphthalmia with RP, which, in this population study, represented 3% of all RP cases. Hermann’s patients showed a variety of fundus pigmentary abnormalities with or without the typical bone spicule pigmentary changes commonly associated with RP and seen in our case. However, many of these patients had moderate myopia, unlike our patient. In 1965, Franceschetti and Gernet2 reported a presumed autosomal-recessive pedigree (MIM #251700) of microphthalmia without microcornea associated with macrophakia, high hyperopia, a retinal dystrophy, and narrow angle glaucoma. Unlike our patient, these individuals also had dental anomalies and a fundus more reminiscent of fundus flavimaculatus or fundus albipunctatus. In addition, the ERG was variably affected, dark adaptation was normal, and cystoid macular edema may have been present. The consanguineous family reported by MacKay and coworkers,7 demonstrating pseudodominant autosomal-recessive inheritance, also had a cystic macular degeneration that showed no leakage on fluorescein angiography. With age, the cysts resolved, leaving a pigmentary maculopathy. Although these patients also showed narrow/closed-angle glaucoma, microphthalmia, and a pigmentary midperipheral retinopathy similar to those seen in our patient, vitreous abnormalities and normal corneal diameters were seen. In their pedigree consistent with autosomal-recessive inheritance, patients with nanophthalmia, as discussed by Cross and Yoder,6 were also found to have abnormalities of the retinal pigment epithelium and choroid by angiography, which were described on clinical examination as “mottling” of the retinal pigmentation. Perhaps the case report that provides the closest correlation to our patient is the sporadic case of Ghose and coworkers.3 Their 56-year-old male had closed-angle glaucoma, nanophthalmos, microcornea, and a similar retinal appearance. Unfortunately, ERG data are incomplete other than to state that the responses were subnormal through an undilated pupil. No mention is made of the presence of optic nerve drusen, although the nerve is called “hypermetropic” with “mild pallor” and “normal cup– disc ratios.” Optic disc drusen occur in 0.34% of individuals and may be inherited in an autosomal-dominant fashion with variable penetrance or autosomal recessive.4 Optic discs containing drusen are often described as small and crowded, lacking a physiologic cup. This anatomic arrangement may well predispose to the formation of optic disc drusen, which are thought to be the result of a disturbance of axoplasmic transport at the lamina cribrosa, resulting in the extrusion of mitochondria filled with calcium crystals.11 Interestingly, optic disc drusen have been reported to occur in association with hypermetropia.12 Considering the pathogenesis of optic disc drusen, the nanophthalmic eye with its short axial length and thickened sclera seems predisposed to this condition.
To our knowledge, this is the first report of the association of nanophthalmos and optic disc drusen. Optic disc drusen have also been reported to occur in association with RP4,13,14 and angioid streaks.15 In a review of 262 patients with RP, the frequency of optic nerve or parapapillary drusen was 9.2%.13 Edwards et al14 reported the frequency in Usher syndrome to be 8% to 35%. In an exhaustive review of the 41 cases of RP with optic nerve drusen reported up to 1966 by Lorentzen,4 none were found to have nanophthalmos or microphthalmos. The cause of nanophthalmos has been debated. Studies have suggested an abnormality of collagen fibril formation, fibronectin production, or other primary abnormalities related to collagen production and aggregation, which may have secondary effects on, or be related to, primary defects of proteoglycan and/or glycosaminoglycan production and metabolism.8,10 Other disorders of collagen production, such as Stickler syndrome, may also be associated with a retinal dystrophy. The relationship between collagen disorders and retinal degeneration is not well understood, but may be operant here. We are not aware of any genetic linkage data to suggest a possible locus for nanophthalmos that might allow us to consider the possibility of a contiguous gene syndrome as the cause of concurrence. Similar scleral collagen abnormalities have been reported in Hallerman–Streiff syndrome,10 but to our knowledge no patient with this congenital disorder has also had a tapetoretinal degeneration. Hallerman–Streiff syndrome is associated with microphthalmia and glaucoma, but our patient had neither the other craniofacial stigmata nor cataract.16 One must also consider the possibility of the presence of a prior uveal effusion causing a secondary pseudo-RP after retinal detachment with apoptosis, a mechanism of photoreceptor cell death seen in both RP and retinal detachment.17 Uveal effusion and nonrhegmatogenous retinal detachment may occur spontaneously or as a complication of ocular surgery in nanophthalmos.18 The currently accepted mechanism of uveal effusion is that venous drainage is impaired because of the abnormal sclera.19,20 Our patient also demonstrated unusual scalloped peripheral iridocorneal adhesions. These have previously been noted in cases reported by MacKay et al.7 This finding may be due to a prior episode of complete angle closure secondary to peripheral uveal effusion with rotation of the ciliary body anteriorly. Yet one might not expect an extinguished ERG with a history of progressive visual loss if a uveal effusion with detachment were the cause. Nanophthalmos may also be associated with visual field and acuity loss secondary to either glaucoma or uveal effusions. Optic disc drusen not infrequently result in visual field loss21,22 and less commonly in visual acuity loss.21 Finally, in sporadic cases such as ours, one might consider causes due to nongenetic intrauterine processes. For example, congenital rubella infection is known to be associated with glaucoma, a retinal pigmentary disorder, and microphthalmia. Our patient showed no other stigmata of congenital rubella such as hearing loss, congenital cardiac disease, or congenital cataract. Our patient has posterior synechiae and anterior synechiae, both of which may have been caused by intraocular inflamma-
621
Ophthalmology Volume 106, Number 3, March 1999 tion. It is interesting that Sjo¨gren and Larsson reported microphthalmia with tapetoretinal degeneration in a child with scoliosis and another with associated spastic diplegia.23 Both children had renal disease and both were thought to have possibly been affected as a result of a viral embryopathy. We believe that our patient represents a specific syndrome of nanophthalmos associated with RP and optic nerve drusen. Retinitis pigmentosa is the most likely cause of the decreased visual acuity and field. Our case illustrates the need to consider tapetoretinal degeneration as the cause of visual loss in the patient with nanophthalmia.
References 1. Hermann P. Le syndrome microphtalmie-re´tinite pigmentaireglaucome. Arch Ophthalmol (Paris) 1958;18:17–24. 2. Franceschetti A, Gernet H. Diagnostic ultrasonique d’une microphtalmie sans microcorne´e, avec macrophakie, haute hyperme´tropie associe´e a` une de´ge´nerescence tape´to-re´tinienee, une disposition glaucomateuse et des anomalies dentaires. Arch Ophthalmol (Paris) 1965;25:105–16. 3. Ghose S, Sachdev MS, Kumar H. Bilateral nanophthalmos, pigmentary retinal dystrophy, and angle closure glaucoma—a new syndrome? Br J Ophthalmol 1985;69:624 – 8. 4. Lorentzen SE. Drusen of the optic disk. A clinical and genetic study. Acta Ophthalmol Suppl 1966;90:1–79. 5. Standard for clinical electroretinography. International Standardization Committee. Arch Ophthalmol 1989;107:816 –9. 6. Cross HE, Yoder F. Familial nanophthalmos. Am J Ophthalmol 1976;81:300 – 6. 7. MacKay CJ, Shek MS, Carr RE, et al. Retinal degeneration with nanophthalmos, cystic macular degeneration, and angle closure glaucoma. A new recessive syndrome. Arch Ophthalmol 1987;105:366 –71. 8. Yue BYJT, Kurosawa A, Duvall J, et al. Nanophthalmic sclera. Fibronectin studies. Ophthalmology 1988;95:56 – 60. 9. Good WV, Stern WH. Recurrent nanophthalmic uveal effusion syndrome following laser trabeculoplasty. Am J Ophthalmol 1988;106:234 –5.
622
10. Stewart DH III, Streeten BW, Brockhurst RJ, et al. Abnormal scleral collagen in nanophthalmous: an ultrastructural study. Arch Ophthalmol 1991;109:1017–25. 11. Tso MOM. Pathology and pathogenesis of drusen of the optic nervehead. Ophthalmology 1981;88:1066 – 80. 12. Strassman I, Silverston B, Seelenfreund M, et al. Optic disc drusen and hypermetropia. Metab Pediatr System Ophthalmol 1991;14:37–9. 13. Grover S, Fishman GA, Brown J Jr. Frequency of optic disc or parapapillary nerve fiber layer drusen in retinitis pigmentosa. Ophthalmology 1997;104:295– 8. 14. Edwards A, Grover S, Fishman GA. Frequency of photographically apparent optic disc and parapapillary nerve fiber layer drusen in Usher syndrome. Retina 1996;16:388 –92. 15. Coleman K, Ross MH, Mc Cabe M, et al. Disk drusen and angioid streaks in pseudoxanthoma elasticum. Am J Ophthalmol 1991;112:166 –70. 16. Cohen MM Jr. Hallermann–Streiff syndrome: a review. Am J Med Genet 1991;41:488 –99. 17. Chang CJ, Lai WW, Edward DP, Tso MOM. Apoptotic photoreceptor cell death after traumatic retinal detachment in humans. Arch Ophthalmol 1995;113:880 – 6. 18. Ryan EA, Zwaan J, Chylack LT Jr. Nanophthalmos with uveal effusion. Clinical and embryologic considerations. Ophthalmology 1982;89:1013–7. 19. Shaffer RN. Discussion. Trans Am Ophthalmol Soc 1975;73: 119 –20. Comment on: Trans Am Ophthalmol Soc 1975;73: 97–118. 20. Singh OS, Simmons RJ, Brockhurst RJ, Trempe CL. Nanophthalmos: a perspective on identification and therapy. Ophthalmology 1982;89:1006 –12. 21. Scholl GB, Song HS, Winkler DE, Wray SH. The pattern visual evoked potential and pattern electroretinogram in drusen-associated optic neuropathy. Arch Ophthalmol 1992;110: 75– 81. 22. Moody TA, Irvine AR, Cahn PH, et al. Sudden visual field constriction associated with optic disc drusen. J Clin Neuroophthalmol 1993;13:8 –13. 23. Sjo¨gren T, Larsson T. Microphthalmos and anophthalmos with or without coincident oligophrenia; a clinical and genetic-statistical study. Acta Psychiatr Neurol Suppl 1949;56:1– 103.