Diagnostic and Therapeutic Challenges
Edited by H. Richard McDonald
David Chen, BS, and Dr. Ashvini K. Reddy
T
The patient denied use of tanning agents and tamoxifen. Syphilis serologies, QuantiFERON gold, serum lysozyme, HIV testing, and a chest x-ray were ordered and within normal limits. Serum angiotensin enzyme was elevated at 83 U/L (reference range, 8–53). A brain MRI was also normal. Antiretinal antibody testing was not ordered. The patient has not consented to additional testing. The patient is presented for discussion of diagnosis, evaluation, and management.
his case is submitted by David Chen, and Dr. Ashvini K. Reddy of the Department of Ophthalmology, University of Virginia, Charlottesville, Virginia; commented by Dr. Nikolas J. S. London, San Diego, California.
Case Report Dr. Nikolas J. S. London (San Diego, California): Chen et al present a 36-year-old Latino with good central visual acuity but poor peripheral vision and photophobia. He has a prominent history of substance abuse, admittedly including alcohol, tobacco, and inhalational methamphetamine and cocaine. Intravenous drug abuse was not mentioned but is a possibility. In addition to his visual complaints, he notes night sweats and headaches. The patient’s examination is particularly interesting with a broad ring of perimacular outer retinal/retinal pigment epithelium (RPE) atrophy associated with intraretinal crystal deposition. The crystals are difficult to verify in the photograph. There was no evidence of active inflammation in the eye, either on examination or in his imaging. The fluorescein angiogram revealed a darker choroid that may be due to normal variation in racial RPE pigmentation. The fundus autofluorescence revealed hypoautofluorescence in the area of atrophy consistent with advanced RPE dysfunction and hyperautofluorescence along the borders of atrophy consistent with less advanced dysfunction and concerning for potential disease progression. Spectral domain optical coherence tomography and automated visual fields confirmed outer retinal atrophy and corresponding visual field constriction, respectively. His laboratory testing was inconclusive. He did have an elevated angiotensin-converting enzyme, but this is nonspecific and can be elevated in 5% of the normal population. Liver function testing was not mentioned, but it is
A 36-year-old Hispanic man born in Mexico but now living in Virginia is referred for evaluation of retinal disease. Ophthalmologic history is remarkable for bilateral pterygia. He complains of poor peripheral vision and photophobia of insidious onset. His medical history is remarkable for alcoholic hepatitis secondary to heavy drinking for which he takes no medications. Social history is remarkable for intermittent use of transnasal crystal methamphetamine for 6 years, remote transnasal cocaine use, current tobacco use, and multiple incarcerations for intoxication. He denies BCG vaccination as a child in Mexico and denies any history of sexually transmitted disease or HIV. He is currently married and states he is monogamous. Review of systems is significant for night sweats and headaches. He denies fevers, change in appetite, weight loss, skin changes, and difficulty breathing. Family history is notable for poor vision in a grandmother but is otherwise negative for ophthalmic disease, inflammatory conditions, or malignancy. Visual acuity is 20/25 in the right eye and 20/20 in the left eye. There is no preauricular, postauricular, or cervical lymphadenopathy, and there is no enlargement of the lacrimal gland nor is there an afferent pupillary defect. Slit-lamp examination is significant for bilateral pterygia. The cornea is clear without crystals or keratic precipitates, the anterior chamber is deep and quiet, the iris is round and flat without nodules or transillumination defects, and the lens is clear. Intraocular pressure is normal by applanation. There is no vitritis in either eye. Fundus examination is remarkable for saucerized optic disks bilaterally with ring-shaped areas of outer retinal atrophy and refractile crystals encircling the macula (Figure 1). Optical coherence tomography confirms corresponding outer retinal atrophy with sparing of the central macula (Figure 2). Fluorescein angiography demonstrates a darker choroid with staining of atrophic areas without active vasculitis or petalloid leakage (Figure 3). Fundus autofluorescence is significant for hypoautofluorescence of the atrophic retina with hyperautofluorescent borders (Figure 4). Automated visual fields demonstrate peripheral constriction.
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Fig. 1. Bilateral saucerized optic disks with ring-shaped areas of outer retinal atrophy (A) and intraretinal crystals encircling the macula (B).
reasonable to assume that he has some degree of dysfunction given his alcohol abuse. The two main findings in this case are the outer retinal atrophy and intraretinal crystals. Either could be used to formulate a differential diagnosis, and it is interesting to consider where these differentials might overlap. The differential diagnosis of crystalline retinopathy includes the main categories of druginduced inherited conditions and chronic retinal disease and iatrogenic causes. Inherited crystalline retinopathies include Bietti crystalline retinopathy, cystinosis, oxalosis, Kjellin syndrome, and Sjögren–Larsson syndrome. These conditions are unlikely in our patient. Bietti crystalline retinopathy and cystinosis are associated with crystals in the cornea in addition to the retina; cystinosis and oxalosis are associated with renal failure; and SjogrenLarsson syndrome and Kjellin syndrome both have prominent ocular and extraocular findings that our patient does not have. Several chronic retinal conditions are associated with crystals, including calcified drusen, macular telangiectasis Type II, and chronic retinal detachment. Our patient does not have drusen, telangiectatic vessels, or any evidence of a previous retinal detachment. Iatrogenic conditions associated with crystals include intravitreal triamcinolone acetonide injection and use of a Tano scraper, also both not things our patient was exposed to.
Drug-induced conditions are more plausible and include: 1. Tamoxifen, an antiestrogen medication used in the treatment of breast cancer that is not associated with retinal atrophy and was not taken by our patient; 2. Canthaxanthine, a carotenoid derivative used as an oral tanning agent. This is not associated with retinal atrophy, does not cause field defects, and our patient denies any use; 3. Methoxyflurane is a rarely used inhalational anesthetic that can cause renal failure and intravascular retinal crystals. Although recreational inhalation of methoxyflurane associated with retinal crystals has been reported,1 the overall picture does not fit our patient; 4. Ethylene glycol toxicity, like methoxyflurane, can be associated with the deposition of intraretinal calcium oxalate crystals. Ethylene glycol is the primary ingredient in antifreeze and is commonly found in homemade alcohol and can also be inhaled. Retinal toxicity is associated with reduced photopic and scotopic electroretinography amplitudes.2 Although our patient has a prominent history of alcohol abuse, retinal toxicity is typically preceded by renal failure, which our patient does not appear to have, the crystals in ethylene glycol retinopathy are predominantly intraarterial and periarterial, whereas our patient’s crystals were
1708 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
2015 VOLUME 35 NUMBER 8
Fig. 2. Outer retinal atrophy adjacent to the temporal arcades but sparing the central macula in the right (A) and left (B) eyes. Hyperreflective material can be seen in the atrophic areas (C).
extravascular, and ethylene glycol toxicity is not associated with outer retinal atrophy. 5. Talc retinopathy is associated with chronic intravenous drug abuse, which this patient could be withholding, but talc crystals are seen in the small caliber vessels of the macula, and retinopathy may be associated with a peripheral vasculopathy similar to sickle cell retinopathy. Talc retinopathy is also not associated with outer retinal atrophy; 6. Ritonavir retinopathy is a rare condition described in only a handful of patients with HIV/AIDS and liver dysfunction on the protease inhibitor ritonavir.3
Fig. 3. Staining of atrophic areas on fluorescein angiography.
Findings include prominent macular retinal pigment epitheliopathy, possibly in a bull’s eye pattern, intraretinal crystal deposits, and parafoveal telangiectasis. With retinal crystals, outer retinal atrophy, and presumed liver dysfunction, this would be an interesting consideration for our patient if it were not for the fact that he has not taken ritonavir, has perimacular as opposed to macular atrophy, and has no telangiectasis. Still, it illustrates the possibility of an unknown toxic exposure. None of the above diagnoses fit perfectly, pushing us to instead consider the differential diagnosis for
DIAGNOSTIC AND THERAPEUTIC CHALLENGES
1709
Fig. 4. Marked hypoautofluorescence of atrophic retina with hyperautofluorescent borders.
the outer retinal atrophy. This includes macular degeneration, choroidal sclerosis dystrophies including gyrate atrophy, retinitis pigmentosa, rod–cone dystrophies, central areolar choroidal dystrophy, chloroquine or hydroxychloroquine toxicity, Stargardt disease, clofazimine toxicity, and enhanced S-cone syndrome (ESCS). Atypical age-related macular degeneration is unlikely given our patient’s age. Gyrate atrophy is intriguing, as it presents in the second or third decade with visual field restriction and progressive RPE atrophy in the midperiphery; however, the RPE changes are typically in a fairly characteristic scalloped pattern that our patient does not have. Retinitis pigmentosa is certainly possible but typically has pigment clumping and a family history, neither of which are present in this case. Rod–cone dystrophies can have a variable presentation and should be entertained, but the changes typically involve the central macula instead of perimacula. As the name implies, central areolar choroidal dystrophy also preferentially involves the central macula. Chloroquine and hydroxychloroquine toxicity can certainly cause a bull’s eye maculopathy with outer retinal atrophy but take years of exposure, and he has no history of taking either medication. Stargardt disease can also cause a bull’s eye maculopathy and a dark choroid on angiography that this patient had a hint of, but is familial, causes reduced central vision, and presents with prominent pisciform flecks throughout the posterior pole. Clofazimine is an interesting, but unlikely, candidate that has been associated with a large bull’s eye pattern of RPE atrophy and crystal deposition.4,5 It is an antimicrobial that targets bacterial DNA and is used in combination with other medications in the treatment of leprosy and Mycobacterium avium complex infections in patients with HIV/AIDS. Notably, it is associated with crystal deposition in the sclera and iris but not in the retina. Our patient has no history of taking this medication either.
Finally, there is a condition that is more plausible for this patient, ESCS. Enhanced S-cone syndrome is a rare autosomal recessive condition that shares a genetic mutation with Goldmann–Favre syndrome but lacks the vitreous degeneration seen in that condition. Enhanced S-cone syndrome manifests with a ring-like pattern of perimacular pigmentary alterations with a strikingly similar distribution to our patient. Although patients typically have pigment deposition in this area, the clinical phenotype is quite variable, and pigmentary atrophy can also be seen.6,7 Retinal crystals, however, have never been described. The diagnosis is made with electroretinography, which has characteristic changes reflecting a predominance of S cones and near absence of rhodopsin. To summarize the differential diagnosis, nothing fits perfectly. It is possible that the patient either has atypical ESCS, an unknown toxic retinopathy, or a combination of conditions. Enhanced S-cone syndrome is attractive given his age and the distribution of his retinal atrophy. A toxic exposure is attractive because of his social history, potential liver dysfunction, and the relative similarity of other known toxic retinopathies such as ritonavir and clofazimine. Both of these come close to our patient’s findings with outer retinal atrophy and crystals, but for different reasons are not entirely consistent. Ritonavir toxicity has even been noted to cause a bull’s eye maculopathy in a patient without macular telangiectasis, making it even more similar to our patient.8 If possible, electroretinography testing for ESCS, as well as some of the other items on the differential, would be valuable. One could consider a liver function panel as liver dysfunction, which might play a role in toxic retinopathy, as it does with both ritonavir and clofazimine. Furthermore, I would ask about any other potential toxic exposures. As far as treatment is concerned, observation is the most prudent course.
1710 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
Editor’s Note: D. Chen and Dr. A. K. Reddy present a 36-year-old man with a wayward social history, night sweats, good vision, ring-shaped outer retinal atrophy, and refractile crystals encircling the macula. Dr. N. J. S. London has consulted on this case and provided us a differential diagnosis using the differential diagnosis for a outer retinal atrophy and the differential diagnosis for crystalline retinopathy. Bull’s Eye Retinopathy I. Degenerations A. Age-related macular degeneration II. Dystrophies A. Gyrate atrophy B. Retinitis pigmentosa C. Rod–cone D. Central areolar choroidal E. Stargardt disease F. ESCS III. Toxicity A. Chloroquine B. Hydroxychloroquine C. Clofazimine Crystalline Retinopathy I. Genetic A. Bietti’s crystalline retinopathy B. Cystinosis C. Oxalosis D. Kjellin syndrome E. Sjögren–Larsson II. Toxicity A. Tamoxifen B. Canthaxanthine C. Methoxyflurane
2015 VOLUME 35 NUMBER 8
D. Ethylene glycol E. Talc F. Ritonavir Dr. London concludes that nothing is a perfect fit but considers the most likely diagnosis ESCS or a toxic retinopathy due to unknown etiology. In particular, he notes that ritonavir toxicity has been associated with a bull’s eye maculopathy. Therefore, he advises an electroretinogram to investigate ESCS. He also requests liver function studies, as liver dysfunction might play a role in a toxic retinopathy. We thank D. Chen and Dr. A. K. Reddy for their unusual case, and Dr. N. J. S. London for his consultation. References 1. Novak MA, Roth AS, Levine MR. Calcium oxalate retinopathy associated with methoxyflurane abuse. Retina 1988;8:230–236. 2. Rossa V, Weber U. Effect of ethylene glycol on rabbit retinas. Ophthalmologica 1990;200:98–103. 3. Roe RH, et al. Retinal pigment epitheliopathy, macular telangiectasis, and intraretinal crystal deposits in HIV-positive patients receiving ritonavir. Retina 2011;31:559–565. 4. Craythorn JM, Swartz M, Creel DJ. Clofazimine-induced bull’seye retinopathy. Retina 1986;6:50–52. 5. Cunningham CA, Friedberg DN, Carr RE. Clofazamine-induced generalized retinal degeneration. Retina 1990;10:131–134. 6. Yzer S, et al. Expanded clinical spectrum of enhanced S-cone syndrome. JAMA Ophthalmol 2013;31:1324–1330. 7. Audo I, et al. Phenotypic variation in enhanced S-cone syndrome. Invest Ophthalmol Vis Sci 2008;49:2082–2093. 8. Pinto R, et al. Ritonavir and bull’s eye maculopathy: case report. GMS Ophthalmol Cases 2013;3:1–4.
RETINAÒ, The Journal of Retinal and Vitreous Diseases, encourages readers to submit Diagnostic and Therapeutic Challenges to [email protected]. Cases for the Diagnostic and Therapeutic Challenges section should include a detailed history of the patient, the diagnosis, the workup, the management, and finally, the question or questions that the submitter wishes to have answered by the consultants.
Edited by H. Richard McDonald
David Chen, BS, and Dr. Ashvini K. Reddy
T
The patient denied use of tanning agents and tamoxifen. Syphilis serologies, QuantiFERON gold, serum lysozyme, HIV testing, and a chest x-ray were ordered and within normal limits. Serum angiotensin enzyme was elevated at 83 U/L (reference range, 8–53). A brain MRI was also normal. Antiretinal antibody testing was not ordered. The patient has not consented to additional testing. The patient is presented for discussion of diagnosis, evaluation, and management.
his case is submitted by David Chen, and Dr. Ashvini K. Reddy of the Department of Ophthalmology, University of Virginia, Charlottesville, Virginia; commented by Dr. Nikolas J. S. London, San Diego, California.
Case Report Dr. Nikolas J. S. London (San Diego, California): Chen et al present a 36-year-old Latino with good central visual acuity but poor peripheral vision and photophobia. He has a prominent history of substance abuse, admittedly including alcohol, tobacco, and inhalational methamphetamine and cocaine. Intravenous drug abuse was not mentioned but is a possibility. In addition to his visual complaints, he notes night sweats and headaches. The patient’s examination is particularly interesting with a broad ring of perimacular outer retinal/retinal pigment epithelium (RPE) atrophy associated with intraretinal crystal deposition. The crystals are difficult to verify in the photograph. There was no evidence of active inflammation in the eye, either on examination or in his imaging. The fluorescein angiogram revealed a darker choroid that may be due to normal variation in racial RPE pigmentation. The fundus autofluorescence revealed hypoautofluorescence in the area of atrophy consistent with advanced RPE dysfunction and hyperautofluorescence along the borders of atrophy consistent with less advanced dysfunction and concerning for potential disease progression. Spectral domain optical coherence tomography and automated visual fields confirmed outer retinal atrophy and corresponding visual field constriction, respectively. His laboratory testing was inconclusive. He did have an elevated angiotensin-converting enzyme, but this is nonspecific and can be elevated in 5% of the normal population. Liver function testing was not mentioned, but it is
A 36-year-old Hispanic man born in Mexico but now living in Virginia is referred for evaluation of retinal disease. Ophthalmologic history is remarkable for bilateral pterygia. He complains of poor peripheral vision and photophobia of insidious onset. His medical history is remarkable for alcoholic hepatitis secondary to heavy drinking for which he takes no medications. Social history is remarkable for intermittent use of transnasal crystal methamphetamine for 6 years, remote transnasal cocaine use, current tobacco use, and multiple incarcerations for intoxication. He denies BCG vaccination as a child in Mexico and denies any history of sexually transmitted disease or HIV. He is currently married and states he is monogamous. Review of systems is significant for night sweats and headaches. He denies fevers, change in appetite, weight loss, skin changes, and difficulty breathing. Family history is notable for poor vision in a grandmother but is otherwise negative for ophthalmic disease, inflammatory conditions, or malignancy. Visual acuity is 20/25 in the right eye and 20/20 in the left eye. There is no preauricular, postauricular, or cervical lymphadenopathy, and there is no enlargement of the lacrimal gland nor is there an afferent pupillary defect. Slit-lamp examination is significant for bilateral pterygia. The cornea is clear without crystals or keratic precipitates, the anterior chamber is deep and quiet, the iris is round and flat without nodules or transillumination defects, and the lens is clear. Intraocular pressure is normal by applanation. There is no vitritis in either eye. Fundus examination is remarkable for saucerized optic disks bilaterally with ring-shaped areas of outer retinal atrophy and refractile crystals encircling the macula (Figure 1). Optical coherence tomography confirms corresponding outer retinal atrophy with sparing of the central macula (Figure 2). Fluorescein angiography demonstrates a darker choroid with staining of atrophic areas without active vasculitis or petalloid leakage (Figure 3). Fundus autofluorescence is significant for hypoautofluorescence of the atrophic retina with hyperautofluorescent borders (Figure 4). Automated visual fields demonstrate peripheral constriction.
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1707
Fig. 1. Bilateral saucerized optic disks with ring-shaped areas of outer retinal atrophy (A) and intraretinal crystals encircling the macula (B).
reasonable to assume that he has some degree of dysfunction given his alcohol abuse. The two main findings in this case are the outer retinal atrophy and intraretinal crystals. Either could be used to formulate a differential diagnosis, and it is interesting to consider where these differentials might overlap. The differential diagnosis of crystalline retinopathy includes the main categories of druginduced inherited conditions and chronic retinal disease and iatrogenic causes. Inherited crystalline retinopathies include Bietti crystalline retinopathy, cystinosis, oxalosis, Kjellin syndrome, and Sjögren–Larsson syndrome. These conditions are unlikely in our patient. Bietti crystalline retinopathy and cystinosis are associated with crystals in the cornea in addition to the retina; cystinosis and oxalosis are associated with renal failure; and SjogrenLarsson syndrome and Kjellin syndrome both have prominent ocular and extraocular findings that our patient does not have. Several chronic retinal conditions are associated with crystals, including calcified drusen, macular telangiectasis Type II, and chronic retinal detachment. Our patient does not have drusen, telangiectatic vessels, or any evidence of a previous retinal detachment. Iatrogenic conditions associated with crystals include intravitreal triamcinolone acetonide injection and use of a Tano scraper, also both not things our patient was exposed to.
Drug-induced conditions are more plausible and include: 1. Tamoxifen, an antiestrogen medication used in the treatment of breast cancer that is not associated with retinal atrophy and was not taken by our patient; 2. Canthaxanthine, a carotenoid derivative used as an oral tanning agent. This is not associated with retinal atrophy, does not cause field defects, and our patient denies any use; 3. Methoxyflurane is a rarely used inhalational anesthetic that can cause renal failure and intravascular retinal crystals. Although recreational inhalation of methoxyflurane associated with retinal crystals has been reported,1 the overall picture does not fit our patient; 4. Ethylene glycol toxicity, like methoxyflurane, can be associated with the deposition of intraretinal calcium oxalate crystals. Ethylene glycol is the primary ingredient in antifreeze and is commonly found in homemade alcohol and can also be inhaled. Retinal toxicity is associated with reduced photopic and scotopic electroretinography amplitudes.2 Although our patient has a prominent history of alcohol abuse, retinal toxicity is typically preceded by renal failure, which our patient does not appear to have, the crystals in ethylene glycol retinopathy are predominantly intraarterial and periarterial, whereas our patient’s crystals were
1708 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
2015 VOLUME 35 NUMBER 8
Fig. 2. Outer retinal atrophy adjacent to the temporal arcades but sparing the central macula in the right (A) and left (B) eyes. Hyperreflective material can be seen in the atrophic areas (C).
extravascular, and ethylene glycol toxicity is not associated with outer retinal atrophy. 5. Talc retinopathy is associated with chronic intravenous drug abuse, which this patient could be withholding, but talc crystals are seen in the small caliber vessels of the macula, and retinopathy may be associated with a peripheral vasculopathy similar to sickle cell retinopathy. Talc retinopathy is also not associated with outer retinal atrophy; 6. Ritonavir retinopathy is a rare condition described in only a handful of patients with HIV/AIDS and liver dysfunction on the protease inhibitor ritonavir.3
Fig. 3. Staining of atrophic areas on fluorescein angiography.
Findings include prominent macular retinal pigment epitheliopathy, possibly in a bull’s eye pattern, intraretinal crystal deposits, and parafoveal telangiectasis. With retinal crystals, outer retinal atrophy, and presumed liver dysfunction, this would be an interesting consideration for our patient if it were not for the fact that he has not taken ritonavir, has perimacular as opposed to macular atrophy, and has no telangiectasis. Still, it illustrates the possibility of an unknown toxic exposure. None of the above diagnoses fit perfectly, pushing us to instead consider the differential diagnosis for
DIAGNOSTIC AND THERAPEUTIC CHALLENGES
1709
Fig. 4. Marked hypoautofluorescence of atrophic retina with hyperautofluorescent borders.
the outer retinal atrophy. This includes macular degeneration, choroidal sclerosis dystrophies including gyrate atrophy, retinitis pigmentosa, rod–cone dystrophies, central areolar choroidal dystrophy, chloroquine or hydroxychloroquine toxicity, Stargardt disease, clofazimine toxicity, and enhanced S-cone syndrome (ESCS). Atypical age-related macular degeneration is unlikely given our patient’s age. Gyrate atrophy is intriguing, as it presents in the second or third decade with visual field restriction and progressive RPE atrophy in the midperiphery; however, the RPE changes are typically in a fairly characteristic scalloped pattern that our patient does not have. Retinitis pigmentosa is certainly possible but typically has pigment clumping and a family history, neither of which are present in this case. Rod–cone dystrophies can have a variable presentation and should be entertained, but the changes typically involve the central macula instead of perimacula. As the name implies, central areolar choroidal dystrophy also preferentially involves the central macula. Chloroquine and hydroxychloroquine toxicity can certainly cause a bull’s eye maculopathy with outer retinal atrophy but take years of exposure, and he has no history of taking either medication. Stargardt disease can also cause a bull’s eye maculopathy and a dark choroid on angiography that this patient had a hint of, but is familial, causes reduced central vision, and presents with prominent pisciform flecks throughout the posterior pole. Clofazimine is an interesting, but unlikely, candidate that has been associated with a large bull’s eye pattern of RPE atrophy and crystal deposition.4,5 It is an antimicrobial that targets bacterial DNA and is used in combination with other medications in the treatment of leprosy and Mycobacterium avium complex infections in patients with HIV/AIDS. Notably, it is associated with crystal deposition in the sclera and iris but not in the retina. Our patient has no history of taking this medication either.
Finally, there is a condition that is more plausible for this patient, ESCS. Enhanced S-cone syndrome is a rare autosomal recessive condition that shares a genetic mutation with Goldmann–Favre syndrome but lacks the vitreous degeneration seen in that condition. Enhanced S-cone syndrome manifests with a ring-like pattern of perimacular pigmentary alterations with a strikingly similar distribution to our patient. Although patients typically have pigment deposition in this area, the clinical phenotype is quite variable, and pigmentary atrophy can also be seen.6,7 Retinal crystals, however, have never been described. The diagnosis is made with electroretinography, which has characteristic changes reflecting a predominance of S cones and near absence of rhodopsin. To summarize the differential diagnosis, nothing fits perfectly. It is possible that the patient either has atypical ESCS, an unknown toxic retinopathy, or a combination of conditions. Enhanced S-cone syndrome is attractive given his age and the distribution of his retinal atrophy. A toxic exposure is attractive because of his social history, potential liver dysfunction, and the relative similarity of other known toxic retinopathies such as ritonavir and clofazimine. Both of these come close to our patient’s findings with outer retinal atrophy and crystals, but for different reasons are not entirely consistent. Ritonavir toxicity has even been noted to cause a bull’s eye maculopathy in a patient without macular telangiectasis, making it even more similar to our patient.8 If possible, electroretinography testing for ESCS, as well as some of the other items on the differential, would be valuable. One could consider a liver function panel as liver dysfunction, which might play a role in toxic retinopathy, as it does with both ritonavir and clofazimine. Furthermore, I would ask about any other potential toxic exposures. As far as treatment is concerned, observation is the most prudent course.
1710 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
Editor’s Note: D. Chen and Dr. A. K. Reddy present a 36-year-old man with a wayward social history, night sweats, good vision, ring-shaped outer retinal atrophy, and refractile crystals encircling the macula. Dr. N. J. S. London has consulted on this case and provided us a differential diagnosis using the differential diagnosis for a outer retinal atrophy and the differential diagnosis for crystalline retinopathy. Bull’s Eye Retinopathy I. Degenerations A. Age-related macular degeneration II. Dystrophies A. Gyrate atrophy B. Retinitis pigmentosa C. Rod–cone D. Central areolar choroidal E. Stargardt disease F. ESCS III. Toxicity A. Chloroquine B. Hydroxychloroquine C. Clofazimine Crystalline Retinopathy I. Genetic A. Bietti’s crystalline retinopathy B. Cystinosis C. Oxalosis D. Kjellin syndrome E. Sjögren–Larsson II. Toxicity A. Tamoxifen B. Canthaxanthine C. Methoxyflurane
2015 VOLUME 35 NUMBER 8
D. Ethylene glycol E. Talc F. Ritonavir Dr. London concludes that nothing is a perfect fit but considers the most likely diagnosis ESCS or a toxic retinopathy due to unknown etiology. In particular, he notes that ritonavir toxicity has been associated with a bull’s eye maculopathy. Therefore, he advises an electroretinogram to investigate ESCS. He also requests liver function studies, as liver dysfunction might play a role in a toxic retinopathy. We thank D. Chen and Dr. A. K. Reddy for their unusual case, and Dr. N. J. S. London for his consultation. References 1. Novak MA, Roth AS, Levine MR. Calcium oxalate retinopathy associated with methoxyflurane abuse. Retina 1988;8:230–236. 2. Rossa V, Weber U. Effect of ethylene glycol on rabbit retinas. Ophthalmologica 1990;200:98–103. 3. Roe RH, et al. Retinal pigment epitheliopathy, macular telangiectasis, and intraretinal crystal deposits in HIV-positive patients receiving ritonavir. Retina 2011;31:559–565. 4. Craythorn JM, Swartz M, Creel DJ. Clofazimine-induced bull’seye retinopathy. Retina 1986;6:50–52. 5. Cunningham CA, Friedberg DN, Carr RE. Clofazamine-induced generalized retinal degeneration. Retina 1990;10:131–134. 6. Yzer S, et al. Expanded clinical spectrum of enhanced S-cone syndrome. JAMA Ophthalmol 2013;31:1324–1330. 7. Audo I, et al. Phenotypic variation in enhanced S-cone syndrome. Invest Ophthalmol Vis Sci 2008;49:2082–2093. 8. Pinto R, et al. Ritonavir and bull’s eye maculopathy: case report. GMS Ophthalmol Cases 2013;3:1–4.
RETINAÒ, The Journal of Retinal and Vitreous Diseases, encourages readers to submit Diagnostic and Therapeutic Challenges to [email protected]. Cases for the Diagnostic and Therapeutic Challenges section should include a detailed history of the patient, the diagnosis, the workup, the management, and finally, the question or questions that the submitter wishes to have answered by the consultants.
