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Disc swelling in an adult diabetic patient
SURVEY OF OPHTHALMOLOGY VOLUME 35 - NUMBER 2 - sEPTMBER-OCTOBER 1990
CLINICAL CHALLENGES,
RONALD M . BURDE, EDITOR
Disc Swelling in an Adult Diabetic Patient BARRETT KATZ, M .D.
Pacific Presbyterian Medical Center and The Smith-Kettlewell Eye Research Institute, San Francisco, California
Comments by Lyn A . Sedwick, M.D ., Michael Slavin, M.D ., and Michael Wall, M .D .
(In keeping with the purpose of a clinical pathological conference, the abstract and key words appear at the end of the article .)
Case Report : This 58-year-old South American-
blurring of the peripapillary retinal nerve fiber lay-
born right-handed mildly obese woman was followed in our general medical clinics for adult onset insulin dependent non-ketotic prone diabetes, first recognized at age 40 . She had been seen for systemic manifestations of her glucose intolerance, includ-
er, with loss of superficial linear light reflexes . Disc margins were blurred, with nerve fiber layer hemorrhages off of each disc surface . Venous pulsations were easily visible on each side (Fig . 1) . Fluorescein angiography demonstrated minimal background diabetic retinopathy without neovascular change . Early phases of the angiogram demonstrated dilation of the vessels on the surface of each disc ; later phases demonstrated hyperfluorescence of each disc with leakage of dye into the peripapillary retina and the disc itself Visual field examination demonstrated mild enlargement of each blind spot and scattered areas of focal depression in an arcuate distribution most prominent in the inferior nasal quadrants .
ing diabetic peripheral neuropathy, background retinopathy, and nephropathy, though without frank renal failure or uremia . She had mild hypertension . In the course of routine retinal billow-up for her background diabetic retinopathy, it was noted that her optic discs appeared swollen- She denied headache or other neurologic signs or symptoms and denied transient obscurations of vision . The patient was referred for evaluation of her disc edema . When first seen by the Neuro-Ophthalmology Service, she was noted to have central acuity of
The patient was evaluated for the etiology of tier disc edema . Medical evaluation revealed borderline renal function and glucose intolerance with a normal ESR and negative syphilis serologies . Analysis of the CSF was entirely within normal limits, with opening pressure of 160 mm of water . Neurologic evaluation revealed only the peripheral neuropathy consistent with diabetes, with normal MRI and CT scanning of intracranial contents . No concomitant endocrine, metabolic, collagen vascular or other systemic illness could be recognized- The patient was followed for the next four months with persist-
20/20 OD, 20/25 OS, with normal color vision bilaterally . Pupils were sluggish but without relative afferent defect . Intraocular pressures were in the low twenties bilaterally . Anterior segments were unremarkably normal except for changes of early nuclear sclerosis bilaterally . No rubeosis was noted either at the pupillary margin or within angle structures . Evaluation of the posterior pole revealed mild disc edema associated with hyperemia and surface telangiectatic capillarity . There was 158
DISC SWELLING IN AN ADULT DIABETIC PATIENT
159
Fig . 1 .
Right and left furidus photographs demonstrating minimal disc swelling, no central cup, and background diabetic retinopathy .
ing low-grade disc edema with preserved spontaneous venous pulsations . What is your presumptive diagnosis? What is the relationship of her diabetes to her disc edema? Comments Comments by LynA . Sedwick, M .D ., Neuro-ophthalmology, Florida Hospital, Orlando, Florida This 58-year-old woman with diabetes developed bilateral, mild disc edema without evidence of flagrant optic nerve dysfunction, namely, abnormal visual acuity, visual fields or both . Her work-up included intravenous fluorescein angiogram which showed leakage at the optic nerve heads . She also underwent computerized tomographic and magnetic resonance scanning of her head and orbits which was normal. Laboratory tests including renal function studies and serologies were normal . Lumbar puncture was normal as well . Four months later, she continued to demonstrate disc edema with spontaneous venous pulsations seen . A number of conditions can cause bilateral disc edema . Usually these conditions can be easily differentiated by history or examination . In children, optic nerve drusen may be present as swollen discs before the characteristic "ice cubes" stick out of the disc surface . Also in children, papillitis may be bilateral and is usually associated with an infectious disease . Leukemia or lymphoma may involve the optic disc or discs, as may sarcoidosis . Any ocular inflammation, such as pars planitis, may give bilateral disc edema as may any bilateral orbital congestive disorder, such as thyroid eye disease or carotid-cavernous fistula . Uncontrolled hypertension may cause bilateral disc edema as can uremia, sometimes associated with a reversible visual loss .' Hayreh has reported patients with acute ischemic optic neuropathy in one eye and asymptomatic disc :
edema in the fellow eyes The patient under discussion does not have good historical, clinical, or laboratory evidence for any of the above entities . Given the lack of raised intracranial pressure during lumbar puncture or evidence of meningitis or hydrocephalus, the best explanation for her findings seems to be diabetic papillopathy, defined as unilateral or bilateral disc edema with or without decreased visual function, all of which generally improves with time . The best recent accounts of such patients are those by Barr et ate and Pavan et at' in 1980 . Two analogous cases were described by Slavin in 1987 ." It is not clear what diabetic papillopathy is . It may be an aborted form of ischemic optic neuropathy, as Dr . Slavin believes, or a "vasculopathy of the most superficial layers of capillaries," as Dr . Pavan et al postulate . This entity is usually diagnosed in young patients with diabetes, i .e ., in their teens or 20s, and resolves within 3-6 months . It is not clear what relationship the diabetes has to the disc edema . Given this patient's age, diabetic papillopathy would be a very tenuous diagnosis and this would merit close follow-up and appropriate retesting for some better explanation for the clinical findings, should they persist . Comments by Michael L . Slavin, M .D., Associate Professor of Ophthalmology, Albert Einstein College of Medicine, Long Island Jewish Hospital, New Hyde Park, Long Island, New York The case for discussion is a 58-year-old obese, hypertensive woman with an 18-year history of insulin-dependent diabetes mellitus, who was found to have bilateral optic disc edema and background diabetic retinopathy without visual symptoms . Systemic manifestations of diabetes included nephropathy and peripheral neuropathy . The etiology of the disc edema is sought as well as the possible relationship of the edema to the diabetes .
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Surv Ophthalmol 35 (2) September-October 1990
The bilateral optic disc edema in this case could represent: 1) papilledema due to a space occupying intracranial lesion or an inflammatory/infectious process ; 2) increased intracranial pressure due to pseudotumor cerebri ; or 3) the syndrome of optic neuropathy associated with diabetes mellitus . If the mild bilateral optic disc edema in this case represents early papilledema (due to a space occupying lesion or pseudotumor cerebri), signs of optic nerve dysfunction (decreased pupillary light reflex or afferent pupil defect, visual field defect other than enlargement of the blind spot, or color vision defect) should not be evident . At a later stage, postpapilledema optic atrophy may ensue with progressive visual loss typically first involving peripheral fields . The focal visual field depression paracentrally in the inferonasal quadrants bilaterally in this case would be atypical for papilledema at this stage . In addition, the pupillary reactions were stated to be "sluggish ." This finding may be explained by a bilateral optic neuropathy, but could represent efferent pathway dysfunction, i .e ., a neuropathy of the short ciliary nerves or a tonic pupil due to diabetes. The evaluation of pupillary constriction to a near stimulus would be useful in differentiating these possibilities (i .e ., with optic neuropathy or tonic pupil, the near pupil reaction would be more brisk than the light reflex) . Computed tomography and magnetic resonance imaging excluded a space occupying lesion . The diagnosis of papilledema due to pseudotumor cerebri is unlikely for several other reasons . 1) Spontaneous venous pulsations were seen on initial examination and on follow-up examinations over a four month period . 2) The opening pressure on lumbar puncture was 160 mm of water which is well within normal limits . One proviso, however, is necessary before dismissing the possibility of pseudotumor cerebri based on the latter two factors . Occasionally, patients with pseudotumor cerebri will have an opening pressure on lumbar puncture within the normal range . This may reflect a sampling phenomenon due to the diurnal fluctuation of intracranial pressure . Indeed, a patient with known pseudotumor cerebri with an intracranial pressure monitor was found to have fluctuation of intracranial pressure ranging from 50 mm to 500 mm of water over a 24-hour period ." In Dr . Katz's case, however, spontaneous venous pulsations over a four-month period persisted . This indicates that the intracranial pressure at each time was below approximately 200 mm of water when intraocular pressure is normal . In summary, pseudotumor cerebri would be unlikely due to the pupil disturbance, visual field defects, persistent spontaneous retinal venous pulsations, and the normal result of the opening pressure on lumbar puncture .
KATZ
The optic disc edema and minimal visual dysfunction seen initially in this case are most compatible with the syndrome of optic neuropathy associated with diabetes mellitus .""' Lubow and Makleys in 1971 reported three patients with juvenile onset diabetes, who developed bilateral optic disc edema simulating papilledema . In one case, no objective visual dysfunction was noted and symptoms consisted of visual obscurations . In a second case, minimal visual acuity and visual field defects occurred with spontaneous improvement of both visual function and optic disc edema six months later . Barr et a12 reported 12 patients with juvenile onset diabetes (11 patients, aged 15-29 and one patient 52 years old) who developed bilateral optic disc edema associated with minimal acuity or visual field defects which most often recovered . The optic disc edema did not correlate with the degree of background diabetic retinopathy . The etiology of the optic disc edema is unclear, but is thought to be either due to a reversible vasculopathy or due to a metabolic disturbance . The optic disc edema associated with diabetes mellitus should not be confused with neovascularization of the optic disc seen with proliferative retinopathy. In 1987,1 reported two cases of chronic asymptomatic ischemic optic neuropathy in adults with diabetes mellitus ." Those two patients had a clinical course similar to that of the numerous patients reported with juvenile onset diabetes and optic disc edema . Occasionally, asymptomatic optic disc edema may be seen in the fellow eye of a patient with typical anterior ischemic optic neuropathy .' The disc edema is thought to be due to axoplasmic transport blockage from low grade ischemia which is insufficient to produce visual dysfunction . Comments by Michael Wall, M .D ., Associate Professor of Neurology and Ophthalmology, Tulane University School of Medicine, New Orleans, Louisiana
The patient is a 58-year-old mildly obese woman with adult onset diabetes mellitus and mild arterial hypertension, referred for evaluation of bilateral disc edema . On examination she has pupils that react sluggishly to light . Disc edema, associated with venous pulsations, is present bilaterally . Visual field examination shows enlargement of the blind spots and arcuate nerve fiber bundle defects, especially in the inferior nasal quadrants . Her evaluation shows normal intracranial pressure and she does not have any of the diseases known to cause elevated intracranial pressure . She has spontaneous venous pulsations ; however, her intraocular pressure is mildly elevated . Elevated intraocular pressure may bring out venous pulsations when intracranial pressure is elevated (like pressing
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DISC SWELLING IN AN ADULT DIABETIC PATIENT
on the globe) . In addition, the CSF pressure may vary from normal to elevated throughout the day . Therefore, the presence of venous pulsations does not rule out elevated intracranial pressure another time during the day . This single CSF pressure measurement is similar to taking the temperature one time during the course of an illness . For the initial onset of idiopathic intracranial hypertension this patient is old at age 58 . However, this diagnosis remains a prominent consideration because of her obesity, disc edema and the presence of inferior nasal nerve fiber bundle defects . Her testing for systemic illness was negative . Syphilis should be considered because of the light-near dissociation and optic neuropathy . However, her syphilis serology is negative and the light-near dissociation is most likely due to her diabetes mellitus . One should consider diabetic pseudopapilledema . s However, this occurs in the juvenile rather than the adult form of diabetes mellitus . In addition, telangiectatic vessels on the optic disc are usually very prominent in diabetic pseudopapilledema . Adult diabetics with disc edema usually have ischemic optic neuropathy . This is rarely bilateral . Nerve fiber bundle patterns of visual field loss (usually inferior altitudinal type) are present to a more marked degree in ischemic optic neuropathy than in this patient .
Patient Follow-up Background retinopathy progressed to preproliferative stages, with focal areas of capillary nonperfusion documented by fluorescein angiography . Although the disc edema persisted, the patient continued to deny headache . As her retinopathy progressed, she developed macular edema with mild loss of central vision and field consistent with her underlying diabetic retinopathy . She underwent panretinal photocoagulation therapy for preproliferative changes, accomplished successfully and without untoward result . She continued to be followed for an additional 12 months with persisting disc edema . Although she continued to be stoic, vague complaints of headache emerged and the appearance of her optic nerve heads changed . The disc swelling became much more obvious and accompanied by engorgement of the venous side of the retinal vasculature . There were numerous splinter hemorrhages on and adjacent to each disc with grossly elevated disc margins, microaneurysmalformation and progressive capillary dilation of the surface vascularity . Larger surface vessels were obscured by the peripapillary nerve fiber layer as these vessels crossed the disc surface . Numerous flame-shaped hemorrhages and cotton wool spots were apparent, and Patton's lines could be recog-
nized . Spontaneous venous pulsations were lost and could not be easily elicited with digital pressure (Fig . 2) . The patient was re-evaluated neurologically . Her neurologic examination was as before, demonstrating only peripheral neuropathic changes . Her intracranial contents were again scanned, without abnormality . Upon repeat lumbar puncture, however, she was documented to have raised intracranial pressure (opening lumbar pressure greater than 500 mm) . What is your diagnosis now? Were we wrong before?
Follow-up Comments Comments by Lyn A . Sedwick, M .D .
With an additional 12 months of follow-up, this woman demonstrated more striking congestive signs at her optic nerve heads and lost her previously noted spontaneous venous pulsations . Re-evaluation again gave a normal computerized tomographic scan of her head, but lumbar puncture showed an opening pressure of 500 . Now it is clear that this patient has papilledema secondary to raised intracranial pressure, apparently without obstructive hydrocephalus . If the spinal fluid is normal in other respects, then she likely has pseudotumor cerebri and thus the initial diagnosis, in retrospect, was wrong. How can a lumbar puncture show normal pressure and spontaneous venous pulsations be present, as was the case with this patient initially, in a patient with papilledema and pseudotumor cerebri? Unfortunately, some patients with pseudotumor cerebri will have a cerebrospinal fluid diurnal pressure curve with peaks and troughs . If you examine the patient during a trough, spontaneous venous pulsations may be seen in the eye reflecting the normal pressure found on cerebrospinal fluid examination . In some cases, 24-hour continuous monitoring of cerebrospinal fluid pressure will be necessary to make the diagnosis, . 12 so the neurologist or ophthalmologist should never be completely dissuaded from the diagnosis of pseudotumor cerebri based on the opening pressure from one lumbar puncture . One other detail may need to be addressed in this case . We are told at the start of her history that this patient comes from South America . If there is an association between her origin and her current disease, one is tempted to postulate that she harbors cysticercosis intracranially and, in fact, may have an arachnoiditis and secondary hydrocephalus to account for her raised intracranial pressure ." Certainly, cerebrospinal fluid cell counts and chemis-
162
KATZ
Surv Ophthalmol 35 (2) September-October 1990
Right and left fundus photographs demonstrating massive disc swelling with superficial hemorrhages and cotton wool spots . Fig . 2 .
tries should have reflected such an infection early on in her work-up . Her computerized tomographic scanning also should have given evidence of hydrocephalus . Thus, although my final diagnosis is benign intracranial hypertension or pseudotumor cerebri with papilledema and initially fluctuating cerebrospinal fluid pressure, I simply wonder whether her origin in an area of high cysticercosis infection is somehow related to her current disease . Comments by Michael A . Slavin, M.D. I believe that Dr . Katz's patient initially had optic disc edema related to a diabetic vasculopathy . This was associated with progressive retinopathy and diffuse retinal ischemia . One year later, the onset of headache, severe optic disc edema, absent spontaneous retinal venous pulsations and high intracranial pressure were compatible with the syndrome of pseudotumor cerebri . I do not know of any association between diabetes mellitus and pseudotumor cerebri . Comments by Michael Wall, M .D . She later developed progressive preproliferative diabetic retinopathy associated with macular edema. She then underwent panretinal photocoagulation therapy for the preproliferative changes, continued to have vision loss along with increased disc edema associated with loss of spontaneous venous pulsations . Repeat lumbar puncture showed an opening pressure of 500 mm of water . Criteria for papilledema are now fulfilled (disc edema due to increased intracranial pressure) . She has had a thorough evaluation for the causes of papilledema, which was negative . Since she is over 50 her evaluation for causes of elevated intracranial pressure should be repeated . If this work-up is unrevealing she falls into the cate-
gory of idiopathic intracranial hypertension (pseudotumor cerebri) 3 and should receive medical therapy with acetazolamide in high doses ." If this fails to improve her vision optic nerve sheath fenestration should be considered .
Closing Discussion The patient was treated medically for raised intracranial pressure, although without resolution of her disc edema or improvement in visual parameters . She was felt to be a medical failure, and underwent lumbar peritoneal shunting with successful lowering of intracranial pressure, improvement of disc edema, and return of spontaneous venous pulsations . Her headaches resolved and her visual parameters stabilized . "Diabetic papillopathy" is a clinical description reported initially in teenage patients with longstanding juvenile diabetes . Its clinical spectrum has over the years expanded . It may occur in other than a pediatric population . Three patients with a presumed diabetic papillopathy of adulthood were reported by Feldon et al in 1985 . 3a These patients were adults with insulin dependent diabetes who had persisting bilateral disc edema, an observation not usually made unless the disc edema is due to raised intracranial pressure . Expanding observations of adult diabetics with otherwise unexplained disc edema seem to give credence to the argument for the existence of a real entity of diabetic papillopathy . How is it different from the other optic neuropathies we commonly see in clinical practice? My reading of the literature suggests that its unique features are : 1) it is commonly bilateral ; 2) it suggests a good prognosis for central vision and field ; 3) it is characterized by a disc edema that shows prominent surface telangiectatic change without
DISC SWELLING IN AN ADULT DIABETIC PATIENT neovascularization ; 4) it is not expected to be followed by dramatic optic atrophy ; and 5) it does not appear to be related to the presence or absence of other diabetic retinopathic changes . If diabetic papillopathy exists, what is its pathophysiology? It may be the declaration of disturbed axoplasmic transport, or a microangiopathy affecting the vascular bed subserving (at least) the distal optic nerve head . The diffuse microvascular abnormalities documented in diabetes would not be expected to spare the vasculature of the distal optic nerve . Such a microangiopathy would be influenced by underlying anatomic factors, such as the crowdedness of the nerve head, the size of its underlying scleral canal, and each patient's unique neurovascular architecture . As well, the optic nerve ought be susceptible to the same hypothesized mechanisms which lead to peripheral diabetic neuropathy, namely, prolonged hyperglycemia, failure of glucose utilization, and chronic relative anoxia . Ischemia of the optic nerve head likely is on occasion another manifestation of the well accepted ischemic declarations of diabetes mellitus . The fact that it presents to us a papillopathy (carrying the signature of optic nerve dysfunction) is not counterintuitive to our understandings of optic nerve disease . Is there some contribution to such a clinical entity from the effects of intracranial pressure transmitted through the neural sheaths of the optic nerves? It seems cavalier to ignore this possibility . It may he that the combination of disturbed axoplasmic flow and underlying microvasculopathic changes of the distal optic nerve in diabetes predisposes that anatomy to further embarrassment at a level of intracranial pressure which a normal nerve could tolerate. That is, it may take a lower level of intracranial pressure to generate disc edema in the diabetic disc . Interestingly, most reported cases of diabetic papillopathy do not have levels of intracranial pressure recorded . The cognescenti of glaucoma have taught us that it is not pressure in isolation which affects distal optic nerve integrity, rather, the combi-
nation of that pressure as expressed within the specific underlying anatomic and physiologic milieu of each pa-
163
tient. A chronically sick optic nerve head will suffer embarrassment to axoplasmic flow with less of an insult than we might at first expect . Perhaps there is some additive deleterious effect to distal nerve integrity from levels of intracranial pressure that are "too high for them," regardless of absolute values . A patient such as this must make us stop and re-examine what we know to be "true ." So what ought the clinician think about "diabetic papillopathy?" Let us think of it as a real entity, yet to be well defined or explained, but always a diagnosis of exclusion .
References 1 . Appen RE, Chandra SR, Klein R, Myers FL : Diabetic papillopathy. Am J Ophthalmol 90 :203-209, 1980 2 . Barr CC, Glaser JS, Blankenship G : Acute disc swelling in juvenile diabetes . Arch Ophthatmul 98:2185-2192,1980 3 . Corbett JJ, Savino PJ, Thompson HS, et at : Visual loss in pseudotumor cerebri . Follow-up of 57 patients from 5 to 41 years and a profile of 14 patients with permanent severe visual loss. Arch Neurol 39,461-474,1982 3a . Feldon SE, Luttrull JK : Diabetic papillopathy of adulthood . Invest Ophthalmol Vis Sci (suppl) 26 :27, 1985 4 . Gucer G, Viernstein L : Long-term intracranial pressure recording in the management of pseudotumor cerebri . 1 Nnerosurg 49:256-263, 1978 5 . Hayreh SS : Anterior ischemic optic neuropathy . V. Optic disc edema as early sign . Arch Ophthalmol 99:1030-1040, 1981 6 . Hoffman HJ : How is pseudotumor cerebri daignosed? Arch Neurof 43 :167-168, 1986 7 . Knox DL, Hanpeken AM, Hollows FC, et al : Uremic optic neuropathy. Arch Ophthalmol 106 :50-54, 1988 8 . LubowM .MakleyTA :Pseudopapilledemaofjuvenile diabetes mellitus . Arch Ophthalmol 85 :417-422, 1971 9 . Pavan PR, Aiello LM, Wafai Z, et al : Optic disc edema in juvenile-onset diabetes. Arch Ophthalmol 98.2193-2195, 1980 10 . Scharf D : Neurocystieercosis : Two hundred thirty-eight cases from a California hospital . Arch Neurol 45 :777-780, 1988 11 . Slavin ML : Chronic asymptomatic ischtmic optic neuropathy : A report of two cases in adults with diabetes mellitus . ./ Giro Neuro Ophlhalmot 7:198-201, 1987 12 . Spence JD, Amacher AL, Willis NR: Benign intracranial hypertension without papilledema : Role of 24-hour cerebrospinal fluid pressure monitoring in diagnosis and management. Neurosurg 7 :326-336, 1980 13 . Wall M, Hart WM. Burde RM : Visual field defects in idiopathic intracranial hypertension (pseudotumor cerebri). Ant J Ophthalmol 96 :654-669, 1983
Reprint address : Barred Katz, M.D ., Dept, of Ophthalmology, Pacific Presbyterian Medical Center, 2340 Clay St ., San Francisco, CA 94120.
Abstract . A patient with insulin dependent adult onset diabetes presented with bilateral disc edema and minimal visual dysfunction . Initial work-up excluded an intracranial lesion, and a lumbar puncture revealed a normal opening pressure . The patient developed proliferative retinopathy, for which she received photocoagulation therapy . She subsequently developed an exacerbation and change of her disc swelling, associated with raised intracranial pressure . The differential diagnosis of diabetic papillopathy and papilledema is discussed . (Sure Ophthalmol 35 :158-163, 1990)
Key words . cerebrospinal fluid pressure • disc swelling • ischemic optic neuropathy
diabetes mellitus papilledema
•
diabetic papillopathy
•
CLINICAL CHALLENGES,
RONALD M . BURDE, EDITOR
Disc Swelling in an Adult Diabetic Patient BARRETT KATZ, M .D.
Pacific Presbyterian Medical Center and The Smith-Kettlewell Eye Research Institute, San Francisco, California
Comments by Lyn A . Sedwick, M.D ., Michael Slavin, M.D ., and Michael Wall, M .D .
(In keeping with the purpose of a clinical pathological conference, the abstract and key words appear at the end of the article .)
Case Report : This 58-year-old South American-
blurring of the peripapillary retinal nerve fiber lay-
born right-handed mildly obese woman was followed in our general medical clinics for adult onset insulin dependent non-ketotic prone diabetes, first recognized at age 40 . She had been seen for systemic manifestations of her glucose intolerance, includ-
er, with loss of superficial linear light reflexes . Disc margins were blurred, with nerve fiber layer hemorrhages off of each disc surface . Venous pulsations were easily visible on each side (Fig . 1) . Fluorescein angiography demonstrated minimal background diabetic retinopathy without neovascular change . Early phases of the angiogram demonstrated dilation of the vessels on the surface of each disc ; later phases demonstrated hyperfluorescence of each disc with leakage of dye into the peripapillary retina and the disc itself Visual field examination demonstrated mild enlargement of each blind spot and scattered areas of focal depression in an arcuate distribution most prominent in the inferior nasal quadrants .
ing diabetic peripheral neuropathy, background retinopathy, and nephropathy, though without frank renal failure or uremia . She had mild hypertension . In the course of routine retinal billow-up for her background diabetic retinopathy, it was noted that her optic discs appeared swollen- She denied headache or other neurologic signs or symptoms and denied transient obscurations of vision . The patient was referred for evaluation of her disc edema . When first seen by the Neuro-Ophthalmology Service, she was noted to have central acuity of
The patient was evaluated for the etiology of tier disc edema . Medical evaluation revealed borderline renal function and glucose intolerance with a normal ESR and negative syphilis serologies . Analysis of the CSF was entirely within normal limits, with opening pressure of 160 mm of water . Neurologic evaluation revealed only the peripheral neuropathy consistent with diabetes, with normal MRI and CT scanning of intracranial contents . No concomitant endocrine, metabolic, collagen vascular or other systemic illness could be recognized- The patient was followed for the next four months with persist-
20/20 OD, 20/25 OS, with normal color vision bilaterally . Pupils were sluggish but without relative afferent defect . Intraocular pressures were in the low twenties bilaterally . Anterior segments were unremarkably normal except for changes of early nuclear sclerosis bilaterally . No rubeosis was noted either at the pupillary margin or within angle structures . Evaluation of the posterior pole revealed mild disc edema associated with hyperemia and surface telangiectatic capillarity . There was 158
DISC SWELLING IN AN ADULT DIABETIC PATIENT
159
Fig . 1 .
Right and left furidus photographs demonstrating minimal disc swelling, no central cup, and background diabetic retinopathy .
ing low-grade disc edema with preserved spontaneous venous pulsations . What is your presumptive diagnosis? What is the relationship of her diabetes to her disc edema? Comments Comments by LynA . Sedwick, M .D ., Neuro-ophthalmology, Florida Hospital, Orlando, Florida This 58-year-old woman with diabetes developed bilateral, mild disc edema without evidence of flagrant optic nerve dysfunction, namely, abnormal visual acuity, visual fields or both . Her work-up included intravenous fluorescein angiogram which showed leakage at the optic nerve heads . She also underwent computerized tomographic and magnetic resonance scanning of her head and orbits which was normal. Laboratory tests including renal function studies and serologies were normal . Lumbar puncture was normal as well . Four months later, she continued to demonstrate disc edema with spontaneous venous pulsations seen . A number of conditions can cause bilateral disc edema . Usually these conditions can be easily differentiated by history or examination . In children, optic nerve drusen may be present as swollen discs before the characteristic "ice cubes" stick out of the disc surface . Also in children, papillitis may be bilateral and is usually associated with an infectious disease . Leukemia or lymphoma may involve the optic disc or discs, as may sarcoidosis . Any ocular inflammation, such as pars planitis, may give bilateral disc edema as may any bilateral orbital congestive disorder, such as thyroid eye disease or carotid-cavernous fistula . Uncontrolled hypertension may cause bilateral disc edema as can uremia, sometimes associated with a reversible visual loss .' Hayreh has reported patients with acute ischemic optic neuropathy in one eye and asymptomatic disc :
edema in the fellow eyes The patient under discussion does not have good historical, clinical, or laboratory evidence for any of the above entities . Given the lack of raised intracranial pressure during lumbar puncture or evidence of meningitis or hydrocephalus, the best explanation for her findings seems to be diabetic papillopathy, defined as unilateral or bilateral disc edema with or without decreased visual function, all of which generally improves with time . The best recent accounts of such patients are those by Barr et ate and Pavan et at' in 1980 . Two analogous cases were described by Slavin in 1987 ." It is not clear what diabetic papillopathy is . It may be an aborted form of ischemic optic neuropathy, as Dr . Slavin believes, or a "vasculopathy of the most superficial layers of capillaries," as Dr . Pavan et al postulate . This entity is usually diagnosed in young patients with diabetes, i .e ., in their teens or 20s, and resolves within 3-6 months . It is not clear what relationship the diabetes has to the disc edema . Given this patient's age, diabetic papillopathy would be a very tenuous diagnosis and this would merit close follow-up and appropriate retesting for some better explanation for the clinical findings, should they persist . Comments by Michael L . Slavin, M .D., Associate Professor of Ophthalmology, Albert Einstein College of Medicine, Long Island Jewish Hospital, New Hyde Park, Long Island, New York The case for discussion is a 58-year-old obese, hypertensive woman with an 18-year history of insulin-dependent diabetes mellitus, who was found to have bilateral optic disc edema and background diabetic retinopathy without visual symptoms . Systemic manifestations of diabetes included nephropathy and peripheral neuropathy . The etiology of the disc edema is sought as well as the possible relationship of the edema to the diabetes .
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Surv Ophthalmol 35 (2) September-October 1990
The bilateral optic disc edema in this case could represent: 1) papilledema due to a space occupying intracranial lesion or an inflammatory/infectious process ; 2) increased intracranial pressure due to pseudotumor cerebri ; or 3) the syndrome of optic neuropathy associated with diabetes mellitus . If the mild bilateral optic disc edema in this case represents early papilledema (due to a space occupying lesion or pseudotumor cerebri), signs of optic nerve dysfunction (decreased pupillary light reflex or afferent pupil defect, visual field defect other than enlargement of the blind spot, or color vision defect) should not be evident . At a later stage, postpapilledema optic atrophy may ensue with progressive visual loss typically first involving peripheral fields . The focal visual field depression paracentrally in the inferonasal quadrants bilaterally in this case would be atypical for papilledema at this stage . In addition, the pupillary reactions were stated to be "sluggish ." This finding may be explained by a bilateral optic neuropathy, but could represent efferent pathway dysfunction, i .e ., a neuropathy of the short ciliary nerves or a tonic pupil due to diabetes. The evaluation of pupillary constriction to a near stimulus would be useful in differentiating these possibilities (i .e ., with optic neuropathy or tonic pupil, the near pupil reaction would be more brisk than the light reflex) . Computed tomography and magnetic resonance imaging excluded a space occupying lesion . The diagnosis of papilledema due to pseudotumor cerebri is unlikely for several other reasons . 1) Spontaneous venous pulsations were seen on initial examination and on follow-up examinations over a four month period . 2) The opening pressure on lumbar puncture was 160 mm of water which is well within normal limits . One proviso, however, is necessary before dismissing the possibility of pseudotumor cerebri based on the latter two factors . Occasionally, patients with pseudotumor cerebri will have an opening pressure on lumbar puncture within the normal range . This may reflect a sampling phenomenon due to the diurnal fluctuation of intracranial pressure . Indeed, a patient with known pseudotumor cerebri with an intracranial pressure monitor was found to have fluctuation of intracranial pressure ranging from 50 mm to 500 mm of water over a 24-hour period ." In Dr . Katz's case, however, spontaneous venous pulsations over a four-month period persisted . This indicates that the intracranial pressure at each time was below approximately 200 mm of water when intraocular pressure is normal . In summary, pseudotumor cerebri would be unlikely due to the pupil disturbance, visual field defects, persistent spontaneous retinal venous pulsations, and the normal result of the opening pressure on lumbar puncture .
KATZ
The optic disc edema and minimal visual dysfunction seen initially in this case are most compatible with the syndrome of optic neuropathy associated with diabetes mellitus .""' Lubow and Makleys in 1971 reported three patients with juvenile onset diabetes, who developed bilateral optic disc edema simulating papilledema . In one case, no objective visual dysfunction was noted and symptoms consisted of visual obscurations . In a second case, minimal visual acuity and visual field defects occurred with spontaneous improvement of both visual function and optic disc edema six months later . Barr et a12 reported 12 patients with juvenile onset diabetes (11 patients, aged 15-29 and one patient 52 years old) who developed bilateral optic disc edema associated with minimal acuity or visual field defects which most often recovered . The optic disc edema did not correlate with the degree of background diabetic retinopathy . The etiology of the optic disc edema is unclear, but is thought to be either due to a reversible vasculopathy or due to a metabolic disturbance . The optic disc edema associated with diabetes mellitus should not be confused with neovascularization of the optic disc seen with proliferative retinopathy. In 1987,1 reported two cases of chronic asymptomatic ischemic optic neuropathy in adults with diabetes mellitus ." Those two patients had a clinical course similar to that of the numerous patients reported with juvenile onset diabetes and optic disc edema . Occasionally, asymptomatic optic disc edema may be seen in the fellow eye of a patient with typical anterior ischemic optic neuropathy .' The disc edema is thought to be due to axoplasmic transport blockage from low grade ischemia which is insufficient to produce visual dysfunction . Comments by Michael Wall, M .D ., Associate Professor of Neurology and Ophthalmology, Tulane University School of Medicine, New Orleans, Louisiana
The patient is a 58-year-old mildly obese woman with adult onset diabetes mellitus and mild arterial hypertension, referred for evaluation of bilateral disc edema . On examination she has pupils that react sluggishly to light . Disc edema, associated with venous pulsations, is present bilaterally . Visual field examination shows enlargement of the blind spots and arcuate nerve fiber bundle defects, especially in the inferior nasal quadrants . Her evaluation shows normal intracranial pressure and she does not have any of the diseases known to cause elevated intracranial pressure . She has spontaneous venous pulsations ; however, her intraocular pressure is mildly elevated . Elevated intraocular pressure may bring out venous pulsations when intracranial pressure is elevated (like pressing
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on the globe) . In addition, the CSF pressure may vary from normal to elevated throughout the day . Therefore, the presence of venous pulsations does not rule out elevated intracranial pressure another time during the day . This single CSF pressure measurement is similar to taking the temperature one time during the course of an illness . For the initial onset of idiopathic intracranial hypertension this patient is old at age 58 . However, this diagnosis remains a prominent consideration because of her obesity, disc edema and the presence of inferior nasal nerve fiber bundle defects . Her testing for systemic illness was negative . Syphilis should be considered because of the light-near dissociation and optic neuropathy . However, her syphilis serology is negative and the light-near dissociation is most likely due to her diabetes mellitus . One should consider diabetic pseudopapilledema . s However, this occurs in the juvenile rather than the adult form of diabetes mellitus . In addition, telangiectatic vessels on the optic disc are usually very prominent in diabetic pseudopapilledema . Adult diabetics with disc edema usually have ischemic optic neuropathy . This is rarely bilateral . Nerve fiber bundle patterns of visual field loss (usually inferior altitudinal type) are present to a more marked degree in ischemic optic neuropathy than in this patient .
Patient Follow-up Background retinopathy progressed to preproliferative stages, with focal areas of capillary nonperfusion documented by fluorescein angiography . Although the disc edema persisted, the patient continued to deny headache . As her retinopathy progressed, she developed macular edema with mild loss of central vision and field consistent with her underlying diabetic retinopathy . She underwent panretinal photocoagulation therapy for preproliferative changes, accomplished successfully and without untoward result . She continued to be followed for an additional 12 months with persisting disc edema . Although she continued to be stoic, vague complaints of headache emerged and the appearance of her optic nerve heads changed . The disc swelling became much more obvious and accompanied by engorgement of the venous side of the retinal vasculature . There were numerous splinter hemorrhages on and adjacent to each disc with grossly elevated disc margins, microaneurysmalformation and progressive capillary dilation of the surface vascularity . Larger surface vessels were obscured by the peripapillary nerve fiber layer as these vessels crossed the disc surface . Numerous flame-shaped hemorrhages and cotton wool spots were apparent, and Patton's lines could be recog-
nized . Spontaneous venous pulsations were lost and could not be easily elicited with digital pressure (Fig . 2) . The patient was re-evaluated neurologically . Her neurologic examination was as before, demonstrating only peripheral neuropathic changes . Her intracranial contents were again scanned, without abnormality . Upon repeat lumbar puncture, however, she was documented to have raised intracranial pressure (opening lumbar pressure greater than 500 mm) . What is your diagnosis now? Were we wrong before?
Follow-up Comments Comments by Lyn A . Sedwick, M .D .
With an additional 12 months of follow-up, this woman demonstrated more striking congestive signs at her optic nerve heads and lost her previously noted spontaneous venous pulsations . Re-evaluation again gave a normal computerized tomographic scan of her head, but lumbar puncture showed an opening pressure of 500 . Now it is clear that this patient has papilledema secondary to raised intracranial pressure, apparently without obstructive hydrocephalus . If the spinal fluid is normal in other respects, then she likely has pseudotumor cerebri and thus the initial diagnosis, in retrospect, was wrong. How can a lumbar puncture show normal pressure and spontaneous venous pulsations be present, as was the case with this patient initially, in a patient with papilledema and pseudotumor cerebri? Unfortunately, some patients with pseudotumor cerebri will have a cerebrospinal fluid diurnal pressure curve with peaks and troughs . If you examine the patient during a trough, spontaneous venous pulsations may be seen in the eye reflecting the normal pressure found on cerebrospinal fluid examination . In some cases, 24-hour continuous monitoring of cerebrospinal fluid pressure will be necessary to make the diagnosis, . 12 so the neurologist or ophthalmologist should never be completely dissuaded from the diagnosis of pseudotumor cerebri based on the opening pressure from one lumbar puncture . One other detail may need to be addressed in this case . We are told at the start of her history that this patient comes from South America . If there is an association between her origin and her current disease, one is tempted to postulate that she harbors cysticercosis intracranially and, in fact, may have an arachnoiditis and secondary hydrocephalus to account for her raised intracranial pressure ." Certainly, cerebrospinal fluid cell counts and chemis-
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Right and left fundus photographs demonstrating massive disc swelling with superficial hemorrhages and cotton wool spots . Fig . 2 .
tries should have reflected such an infection early on in her work-up . Her computerized tomographic scanning also should have given evidence of hydrocephalus . Thus, although my final diagnosis is benign intracranial hypertension or pseudotumor cerebri with papilledema and initially fluctuating cerebrospinal fluid pressure, I simply wonder whether her origin in an area of high cysticercosis infection is somehow related to her current disease . Comments by Michael A . Slavin, M.D. I believe that Dr . Katz's patient initially had optic disc edema related to a diabetic vasculopathy . This was associated with progressive retinopathy and diffuse retinal ischemia . One year later, the onset of headache, severe optic disc edema, absent spontaneous retinal venous pulsations and high intracranial pressure were compatible with the syndrome of pseudotumor cerebri . I do not know of any association between diabetes mellitus and pseudotumor cerebri . Comments by Michael Wall, M .D . She later developed progressive preproliferative diabetic retinopathy associated with macular edema. She then underwent panretinal photocoagulation therapy for the preproliferative changes, continued to have vision loss along with increased disc edema associated with loss of spontaneous venous pulsations . Repeat lumbar puncture showed an opening pressure of 500 mm of water . Criteria for papilledema are now fulfilled (disc edema due to increased intracranial pressure) . She has had a thorough evaluation for the causes of papilledema, which was negative . Since she is over 50 her evaluation for causes of elevated intracranial pressure should be repeated . If this work-up is unrevealing she falls into the cate-
gory of idiopathic intracranial hypertension (pseudotumor cerebri) 3 and should receive medical therapy with acetazolamide in high doses ." If this fails to improve her vision optic nerve sheath fenestration should be considered .
Closing Discussion The patient was treated medically for raised intracranial pressure, although without resolution of her disc edema or improvement in visual parameters . She was felt to be a medical failure, and underwent lumbar peritoneal shunting with successful lowering of intracranial pressure, improvement of disc edema, and return of spontaneous venous pulsations . Her headaches resolved and her visual parameters stabilized . "Diabetic papillopathy" is a clinical description reported initially in teenage patients with longstanding juvenile diabetes . Its clinical spectrum has over the years expanded . It may occur in other than a pediatric population . Three patients with a presumed diabetic papillopathy of adulthood were reported by Feldon et al in 1985 . 3a These patients were adults with insulin dependent diabetes who had persisting bilateral disc edema, an observation not usually made unless the disc edema is due to raised intracranial pressure . Expanding observations of adult diabetics with otherwise unexplained disc edema seem to give credence to the argument for the existence of a real entity of diabetic papillopathy . How is it different from the other optic neuropathies we commonly see in clinical practice? My reading of the literature suggests that its unique features are : 1) it is commonly bilateral ; 2) it suggests a good prognosis for central vision and field ; 3) it is characterized by a disc edema that shows prominent surface telangiectatic change without
DISC SWELLING IN AN ADULT DIABETIC PATIENT neovascularization ; 4) it is not expected to be followed by dramatic optic atrophy ; and 5) it does not appear to be related to the presence or absence of other diabetic retinopathic changes . If diabetic papillopathy exists, what is its pathophysiology? It may be the declaration of disturbed axoplasmic transport, or a microangiopathy affecting the vascular bed subserving (at least) the distal optic nerve head . The diffuse microvascular abnormalities documented in diabetes would not be expected to spare the vasculature of the distal optic nerve . Such a microangiopathy would be influenced by underlying anatomic factors, such as the crowdedness of the nerve head, the size of its underlying scleral canal, and each patient's unique neurovascular architecture . As well, the optic nerve ought be susceptible to the same hypothesized mechanisms which lead to peripheral diabetic neuropathy, namely, prolonged hyperglycemia, failure of glucose utilization, and chronic relative anoxia . Ischemia of the optic nerve head likely is on occasion another manifestation of the well accepted ischemic declarations of diabetes mellitus . The fact that it presents to us a papillopathy (carrying the signature of optic nerve dysfunction) is not counterintuitive to our understandings of optic nerve disease . Is there some contribution to such a clinical entity from the effects of intracranial pressure transmitted through the neural sheaths of the optic nerves? It seems cavalier to ignore this possibility . It may he that the combination of disturbed axoplasmic flow and underlying microvasculopathic changes of the distal optic nerve in diabetes predisposes that anatomy to further embarrassment at a level of intracranial pressure which a normal nerve could tolerate. That is, it may take a lower level of intracranial pressure to generate disc edema in the diabetic disc . Interestingly, most reported cases of diabetic papillopathy do not have levels of intracranial pressure recorded . The cognescenti of glaucoma have taught us that it is not pressure in isolation which affects distal optic nerve integrity, rather, the combi-
nation of that pressure as expressed within the specific underlying anatomic and physiologic milieu of each pa-
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tient. A chronically sick optic nerve head will suffer embarrassment to axoplasmic flow with less of an insult than we might at first expect . Perhaps there is some additive deleterious effect to distal nerve integrity from levels of intracranial pressure that are "too high for them," regardless of absolute values . A patient such as this must make us stop and re-examine what we know to be "true ." So what ought the clinician think about "diabetic papillopathy?" Let us think of it as a real entity, yet to be well defined or explained, but always a diagnosis of exclusion .
References 1 . Appen RE, Chandra SR, Klein R, Myers FL : Diabetic papillopathy. Am J Ophthalmol 90 :203-209, 1980 2 . Barr CC, Glaser JS, Blankenship G : Acute disc swelling in juvenile diabetes . Arch Ophthatmul 98:2185-2192,1980 3 . Corbett JJ, Savino PJ, Thompson HS, et at : Visual loss in pseudotumor cerebri . Follow-up of 57 patients from 5 to 41 years and a profile of 14 patients with permanent severe visual loss. Arch Neurol 39,461-474,1982 3a . Feldon SE, Luttrull JK : Diabetic papillopathy of adulthood . Invest Ophthalmol Vis Sci (suppl) 26 :27, 1985 4 . Gucer G, Viernstein L : Long-term intracranial pressure recording in the management of pseudotumor cerebri . 1 Nnerosurg 49:256-263, 1978 5 . Hayreh SS : Anterior ischemic optic neuropathy . V. Optic disc edema as early sign . Arch Ophthalmol 99:1030-1040, 1981 6 . Hoffman HJ : How is pseudotumor cerebri daignosed? Arch Neurof 43 :167-168, 1986 7 . Knox DL, Hanpeken AM, Hollows FC, et al : Uremic optic neuropathy. Arch Ophthalmol 106 :50-54, 1988 8 . LubowM .MakleyTA :Pseudopapilledemaofjuvenile diabetes mellitus . Arch Ophthalmol 85 :417-422, 1971 9 . Pavan PR, Aiello LM, Wafai Z, et al : Optic disc edema in juvenile-onset diabetes. Arch Ophthalmol 98.2193-2195, 1980 10 . Scharf D : Neurocystieercosis : Two hundred thirty-eight cases from a California hospital . Arch Neurol 45 :777-780, 1988 11 . Slavin ML : Chronic asymptomatic ischtmic optic neuropathy : A report of two cases in adults with diabetes mellitus . ./ Giro Neuro Ophlhalmot 7:198-201, 1987 12 . Spence JD, Amacher AL, Willis NR: Benign intracranial hypertension without papilledema : Role of 24-hour cerebrospinal fluid pressure monitoring in diagnosis and management. Neurosurg 7 :326-336, 1980 13 . Wall M, Hart WM. Burde RM : Visual field defects in idiopathic intracranial hypertension (pseudotumor cerebri). Ant J Ophthalmol 96 :654-669, 1983
Reprint address : Barred Katz, M.D ., Dept, of Ophthalmology, Pacific Presbyterian Medical Center, 2340 Clay St ., San Francisco, CA 94120.
Abstract . A patient with insulin dependent adult onset diabetes presented with bilateral disc edema and minimal visual dysfunction . Initial work-up excluded an intracranial lesion, and a lumbar puncture revealed a normal opening pressure . The patient developed proliferative retinopathy, for which she received photocoagulation therapy . She subsequently developed an exacerbation and change of her disc swelling, associated with raised intracranial pressure . The differential diagnosis of diabetic papillopathy and papilledema is discussed . (Sure Ophthalmol 35 :158-163, 1990)
Key words . cerebrospinal fluid pressure • disc swelling • ischemic optic neuropathy
diabetes mellitus papilledema
•
diabetic papillopathy
•