Diagnostic and Therapeutic Challenges
Edited by H. Richard McDonald
Drs. Tatsuhiko Sato, Kazuyuki Emi, and Arthur D. Fu
T
RRD complicated by proliferative vitreoretinopathy in the right eye at about the age of 13 years. Typically, RRD is not bullous but flat in adolescence or early adulthood because the vitreous gel is not liquefied. Thus, we suspected that he might have an inherited disorder although he did not have any systemic diseases. Another atypical finding was the abnormal postoperative FAF image despite the fundus appearing normal. We were not able to examine the preoperative FAF images because the macula was detached. However, the incidence of a hyperautofluorescent ring in patients with retinitis pigmentosa (RP) has been reported to be over 50%.1–3 The reduction of ERG amplitudes and the annular scotoma are typical clinical signs in cases of RP. Thus, we diagnosed this case as RP accompanied by RRD despite of lacking the classic clinical signs of RP, for example, intraretinal bone-spicule pigment, vessel attenuation, and pale disk.
his case is submitted by Drs. Tatsuhiko Sato and Kazuyuki Emi of the Osaka Rosai Hospital, Clinical Research Center for Occupational Sensory Organ Disability, Kita-ku, Sakai, Japan; commented by Dr. Arthur D. Fu, San Francisco, California. Case Report
A 23-year-old man was referred to our department with a diagnosis of rhegmatogenous retinal detachment (RRD) in his left eye. He did not have any systemic diseases. He had undergone successful vitrectomy for RRD complicated by proliferative vitreoretinopathy in his right eye approximately 10 years earlier. At our initial examination, his decimal best-corrected visual acuity was 0.2 in the right eye and counting finger in the left eye. The intraocular pressures were 13 mmHg in the right eye and 10 mmHg in the left eye. The right eye was aphakic and had undergone panretinal photocoagulation (Figure 1, A and B). The left eye developed bullous retinal detachment (RD) with temporal retinal tears, and the macula was detached (Figure 1, C and D). Ultrawidefield fundus photographs and fundus autofluorescence (FAF) images were taken with the Optos 200Tx (Optos, Scotland, United Kingdom). Combined phacoemulsification and vitrectomy with a 25-gauge system was performed on the left eye under local anesthesia. The vitreous gel was liquefied, and posterior vitreous detachment was already present circumferentially to the retinal tears. Peripheral vitrectomy and vitreous shaving were performed with scleral indentation. Subretinal fluid was drained from the original tears, and fluid–air exchange was performed. Endolaser photocoagulation was applied to the retinal tears and lattice degeneration. The vitreous cavity was filled with 20% sulfur hexafluoride. The retina was reattached, and the decimal best-corrected visual acuity of the left eye improved to 1.2 one month after the vitrectomy. The fundus appeared normal (Figure 2A), but the FAF showed a hyperautofluorescent ring and surrounding granular hypoautofluorescent area along the vascular arcade (Figure 2B). Both the scotopic and photopic electroretinograms (ERGs) recorded with the LE-2000 (Tomey Corporation, Aichi, Japan) were markedly reduced in both eyes (Figure 3, A–D). Goldmann perimetry showed an annular relative scotoma corresponding to the granular hypoautofluorescent area in the left eye (Figure 4). This case had two atypical findings. One was that the vitreous gel of the left eye was liquefied which led to the bullous RD. In addition, he had a clinical history of undergoing vitrectomy for
Dr. Arthur D. Fu (San Francisco, California): The authors present a 23-year-old-man with a history of RD and proliferative vitreoretinopathy in one eye and subsequently developed RD in the fellow eye, successfully repaired with vitrectomy and gas fluid exchange. Intraoperatively, the authors noted vitreous liquefaction and a posterior vitreous detachment suspicious for one at such a young age. Subsequently, FAF demonstrated a ring of hyperautofluorescence, a peculiar granular hypoautofluorescence along the vascular arcades, and severe depression in both rod and cone functions in the repaired fellow eye. We are asked to consider possible diagnoses and to hypothesize the etiology of the autofluorescence patterns. A history of bilateral RD at a relatively young age in concert with prematurely liquified vitreous prompts consideration of inherited RD disorders. Patients with very high myopia are certainly at risk for early syneresis and liquefaction of their vitreous, but a posterior vitreous detachment at a young age is less common. The differential of inherited vitreoretinal degeneration includes Wagner syndrome, erosive vitreoretinopathy (ERVR), Jansen syndrome, Stickler 2153
2154 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
2014 VOLUME 34 NUMBER 10
Fig. 1. Ultrawide-field fundus photographs (A and C) and FAF images (B and D) at the initial visit. A and B. Right eye images. C and D. Left eye images. The white arrows in (C) point to the original retinal tears.
syndrome, snowflake degeneration, Goldmann–Favre syndrome, and Knobloch syndrome. Wagner syndrome, ERVR, and Jansen syndrome are collectively known as 5q retinopathies as they have been localized to the same chromosome and are inherited in an autosomal dominant pattern.4,5 Wagner syndrome is described as an entity that is characterized by an optically empty vitreous with avascular vitreous strands and veils, moderate myopia, presenile cataracts, and retinal degeneration with atrophy. Erosive vitreoretinopathy shares features with Wagner syndrome, including the nyctalopia, constriction of visual fields, chorioretinal atrophy, and propensity for RRD.5 It is important to note that both Wagner syndrome and
Fig. 2. Ultrawide-field fundus photograph (A) and fundus autofluorescence (B) image one month after a vitrectomy for rhegmatogenous retinal detachment in the left eye. The temporal pigmentation is a scar of the endolaser photocoagulation.
ERVR may have electroretinographic abnormalities of both rod and cone functions, but are typically not extinguished. Snowflake vitreoretinal degeneration is not on the 5q chromosome, but shares abnormalities of vitreous and reported risk of RD.6 Characteristic small yellow white deposits in the periphery seen in patients with snowflake vitreoretinal degeneration were not described in our patient. Knobloch syndrome clinical features include smooth (cryptless) irides, high myopia, and vitreoretinal degeneration consisting of diffuse retinal pigment epithelium atrophy with prominent choroidal vessel show, macular atrophic lesions with or without a “punched out” appearance, and white fibrillar
DIAGNOSTIC AND THERAPEUTIC CHALLENGES
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Fig. 3. Full-field ERGs recorded 1 month after the vitrectomy for RRD in the left eye. A. Scotopic ERG. B. Flash ERG. C. Photopic ERG. D. 30-Hz flicker ERG.
vitreous condensations. Systemic features of this autosomal recessive disease include occipital encephalocele. Retinal detachment is a known feature of Knobloch syndrome. Rhegmatogenous retinal detachment in patients with RP (rod or rod–cone dystrophy) is a rare event.7 Case series are limited and associated risk factors include young age and the presence of myopia.7–10 In these younger patients, a common finding is sine pigmenti, or the lack of intraretinal pigment migration or underlying retinal pigment epithelial alteration. It has been hypothesized that adhesions between retinal pigment epithelium and neurosensory retina histologically seen in advanced cases of RP may not be present in younger patients with less severe disease.7 Therefore, younger patients with RP may have no additional protection against RD. Bilateral detachments secondary to giant retina tears in one case series were documented in patients with sensorineural hearing loss, some with clinical features of Usher Syndrome.11,12 In these rare cases, the diagnosis of the RRD preceded the eventual diagnosis of RP. What do the combination of severely depressed ERGs and FAF patterns tell us? Fundus autofluorescence has certainly emerged as an exciting method in characterizing retinal conditions. In RP, a ring of high-density hyperautofluorescence around the fovea indicates a transition from high concentrations of lipofuscin and other fluorophores surrounding more normal central macular retina and retinal pigment epithelium.13–16 Although most commonly described in RP, these parafoveal hyperautofluorescent rings may not be specific to RP. With any relatively new imaging
modality, other entities may yet prove to have a ring of hyperautofluorescence, and published reports of hyperautofluorescent rings are also noted in autoimmune retinopathy. Double hyperautofluorescent rings are noted in Goldmann–Favre syndrome from mutations in the NR2E3 gene.17 Goldmann–Favre syndrome, also thought to be synonymous with enhanced S-cone syndrome, would be a prime candidate. However, a key feature in this disease is an electrophysiologic finding in which photopic and scotopic waveforms are similar, rod-specific function is extremely depressed, and 30-Hz flicker implicit time is delayed. This is seen because of residual S-cone short wavelength activity. However, there is wide phenotypic variability, both in electrophysiologic and clinical findings in patients with NR2E3 mutations. In this patient, the severely depressed rod and cone functions without the finding of similar photopic and scotopic waveforms make it difficult to confirm whether this patient has a form of Goldmann–Favre syndrome. An extensive PubMed review of FAF of Wagner disease and other aforementioned vitreoretinal degenerative syndromes yielded no reports of hyperautofluorescent rings. The hypoautofluorescent areas in a paramacular distribution are also described in patients with RP. Using wide-field FAF, Oishi et al18 characterized hypoautofluorescence in a spectrum corresponding to severity of disease. Smaller, granular, or reticular areas of hypoautofluorescence similar to those seen in our young patient were seen in less severe stages of RP. As the severity increased, patients often developed larger areas of patchy hypoautofluorescence corresponding to visual field deficits. Other forms of
2156 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
2014 VOLUME 34 NUMBER 10
Fig. 4. Goldmann perimetry performed 1 month after the vitrectomy for the RRD in the left eye. The result of perimetry for the left eye is shown on the left side.
“patchy” hypoautofluorescence have been described in choroideremia.19 The combination of severely depressed rod and cone functions on ERG, hyperautofluorescent parafoveal ring, and granular hypoautofluorescent areas suggests an unfortunate patient with RP or Goldmann–Favre syndrome who also was unlucky enough to have bilateral RD. Consideration for genetic testing for the multiple genes associated with RP and NR2E3 mutations should be considered. The nearly undetectable rod function ERGs make vitreoretinal degenerative disorders such as ERVR less likely. However, a careful family history and systemic examination to confirm the presence of any syndromic vitreoretinal degenerative disorders such as Sticklers syndrome, Wagner syndrome, and Knobloch syndrome are advised. Additional genetic testing for 5q chromosomal abnormalities may be necessary to rule out the remote possibility that these conditions also have hyperautofluorescent parafoveal rings and granular hypoautofluorescent rings. Editor’s Note: Drs. Sato and Emi have presented a 23-year-old man with a superior bullous RD in 1 eye and a history of surgery for proliferative vitreoretinopathy 10 years earlier in his other eye. The retina was reattached with good visual recovery, but the FAF revealed unusual macular findings, visual field defects, and reduced ERGs in each eye. The case is presented for discussion of diagnosis, analysis of the autofluorescent findings, and management. Dr. Fu has agreed to consult on this case and addresses the issue of RD at a young age. He notes that
consideration be given to inherited disorders and offers the following differential diagnosis: I. Wagner syndrome II. Erosive vitreoretinopathy III. Jansen syndrome IV. Stickler syndrome V. Snowflake degeneration VI. Goldman–Favre syndrome VII. Knobloch syndrome
He reviews these entities and emphasizes that both Wagner syndrome and ERVR may have abnormalities of both rod and cone functions, but are typically not extinguished. Together these 2 diagnoses, along with Jansen syndrome are known as 5q retinopathies as they are localized to the same chromosome and inherited in an autosomal pattern. Dr. Fu examines the possibility that this patient had RP and states that a lack of intraretinal pigment migration, sine pigmenti, is a common finding in younger patients. Furthermore, he notes the speculation that adhesions between the RPE and neurosensory retina may not be present in younger patients with less severe disease because they are in advanced cases of RP. He addresses the issue of fundus autofluorescent findings. He states that in RP, a ring of high density hyperautofluorescence around the fovea indicates a transition from high concentration of lipofuscin and other fluorophores surrounding more central macular retina and RPE. Similar rings of hyperautofluorescence are noted in Goldman–Favre syndrome from mutations in the NR2E3 gene. Similarly, the paramacular hypoautofluorescent areas are seen in RP. He believes that granular areas of hypoautofluorescence in this young patient are consistent with the reports of less severe stages of RP.
DIAGNOSTIC AND THERAPEUTIC CHALLENGES
Dr. Fu concludes that this patient with bilateral RD has RP and suggests testing for multiple genes associated with RP. He advocates for additional testing for 5q chromosomal abnormalities and for a careful family history and systemic evaluation. We thank Drs. Sato and Emi for their case and Dr. Fu for his consultation. References 1. Robson AG, El-Amir A, Bailey C, et al. Pattern ERG correlates of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity. Invest Ophthalmol Vis Sci 2003;44:3544–3550. 2. Popovic P, Jarc-Vidmar M, Hawlina M. Abnormal fundus autofluorescence in relation to retinal function in patients with retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol 2005; 243:1018–1027. 3. Murakami T, Akimoto M, Ooto S, et al. Association between abnormal autofluorescence and photoreceptor disorganization in retinitis pigmentosa. Am J Ophthalmol 2008;145:687–694. 4. Miyamoto T, Inoue H, Sakamoto Y, et al. Identification of a novel splice site mutation of the CSPG2 gene in a Japanese family with Wagner syndrome. Invest Ophthalmol Vis Sci 2005;46:2726–2735. 5. Brown DM, Kimura AE, Weingeist TA, Stone EM. Erosive vitreoretinopathy. A new clinical entity. Ophthalmology 1994; 101:694–704. 6. Jiao X, Ritter R III, Hejtmancik JF, Edwards AO. Genetic linkage of snowflake vitreoretinal degeneration to chromosome 2q36. Invest Ophthalmol Vis Sci 2004;45:4498–4503. 7. Edwards RS, Calder IG, Crews SJ. Retinal detachment in retinitis pigmentosa. Trans Ophthalmol Soc U K 1985;104:315–318. 8. Johnston GP. Retinitis pigmentosa and retinal detachment. A case report. Retina 1981;1:223–226. 9. Demir MN, Unlu N, Yalniz Z, et al. A case of retinal detachment in retinitis pigmentosa. Eur J Ophthalmol 2007;17: 677–679. 10. Lee SY, Ong SG. Ring retinal detachment in retinitis pigmentosa. Arch Ophthalmol 2006;124:1794.
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11. Kim RY, Schwartz SD, Heckenlively JR, et al. Giant retinal tear and retinal detachment with underlying retinitis pigmentosa and hearing loss. Eye (Lond) 1996;10:697–700. 12. Johnston ME, Gonder JR. Giant retinal tears, retinal detachment and retinitis pigmentosa. Can J Ophthalmol 1985;20:16–18. 13. Robson AG, Egan C, Holder GE, et al. Comparing rod and cone function with fundus autofluorescence images in retinitis pigmentosa. Adv Exp Med Biol 2003;533:41–47. 14. Robson AG, El-Amir A, Bailey C, et al. Pattern ERG correlates of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity. Invest Ophthalmol Vis Sci 2003;44:3544–3550. 15. Robson AG, Saihan Z, Jenkins SA, et al. Functional characterisation and serial imaging of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity. Br J Ophthalmol 2006;90:472–479. 16. Robson AG, Tufail A, Fitzke F, et al. Serial imaging and structure-function correlates of high-density rings of fundus autofluorescence in retinitis pigmentosa. Retina 2011;31:1670–1679. 17. Escher P, Tran HV, Vaclavik V, et al. Double concentric autofluorescence ring in NR2E3-p.G56R-linked autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci 2012;53:4754–4764. 18. Oishi A, Ogino K, Makiyama Y, et al. Wide-field fundus autofluorescence imaging of retinitis pigmentosa. Ophthalmology. 2013;120:1827–1834. 19. Yuan A, Kaines A, Jain A, et al. Ultra-wide-field and autofluorescence imaging of choroidal dystrophies. Ophthalmic Surg Lasers Imaging 2010;41:e1–e5.
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
Drs. Tatsuhiko Sato, Kazuyuki Emi, and Arthur D. Fu
T
RRD complicated by proliferative vitreoretinopathy in the right eye at about the age of 13 years. Typically, RRD is not bullous but flat in adolescence or early adulthood because the vitreous gel is not liquefied. Thus, we suspected that he might have an inherited disorder although he did not have any systemic diseases. Another atypical finding was the abnormal postoperative FAF image despite the fundus appearing normal. We were not able to examine the preoperative FAF images because the macula was detached. However, the incidence of a hyperautofluorescent ring in patients with retinitis pigmentosa (RP) has been reported to be over 50%.1–3 The reduction of ERG amplitudes and the annular scotoma are typical clinical signs in cases of RP. Thus, we diagnosed this case as RP accompanied by RRD despite of lacking the classic clinical signs of RP, for example, intraretinal bone-spicule pigment, vessel attenuation, and pale disk.
his case is submitted by Drs. Tatsuhiko Sato and Kazuyuki Emi of the Osaka Rosai Hospital, Clinical Research Center for Occupational Sensory Organ Disability, Kita-ku, Sakai, Japan; commented by Dr. Arthur D. Fu, San Francisco, California. Case Report
A 23-year-old man was referred to our department with a diagnosis of rhegmatogenous retinal detachment (RRD) in his left eye. He did not have any systemic diseases. He had undergone successful vitrectomy for RRD complicated by proliferative vitreoretinopathy in his right eye approximately 10 years earlier. At our initial examination, his decimal best-corrected visual acuity was 0.2 in the right eye and counting finger in the left eye. The intraocular pressures were 13 mmHg in the right eye and 10 mmHg in the left eye. The right eye was aphakic and had undergone panretinal photocoagulation (Figure 1, A and B). The left eye developed bullous retinal detachment (RD) with temporal retinal tears, and the macula was detached (Figure 1, C and D). Ultrawidefield fundus photographs and fundus autofluorescence (FAF) images were taken with the Optos 200Tx (Optos, Scotland, United Kingdom). Combined phacoemulsification and vitrectomy with a 25-gauge system was performed on the left eye under local anesthesia. The vitreous gel was liquefied, and posterior vitreous detachment was already present circumferentially to the retinal tears. Peripheral vitrectomy and vitreous shaving were performed with scleral indentation. Subretinal fluid was drained from the original tears, and fluid–air exchange was performed. Endolaser photocoagulation was applied to the retinal tears and lattice degeneration. The vitreous cavity was filled with 20% sulfur hexafluoride. The retina was reattached, and the decimal best-corrected visual acuity of the left eye improved to 1.2 one month after the vitrectomy. The fundus appeared normal (Figure 2A), but the FAF showed a hyperautofluorescent ring and surrounding granular hypoautofluorescent area along the vascular arcade (Figure 2B). Both the scotopic and photopic electroretinograms (ERGs) recorded with the LE-2000 (Tomey Corporation, Aichi, Japan) were markedly reduced in both eyes (Figure 3, A–D). Goldmann perimetry showed an annular relative scotoma corresponding to the granular hypoautofluorescent area in the left eye (Figure 4). This case had two atypical findings. One was that the vitreous gel of the left eye was liquefied which led to the bullous RD. In addition, he had a clinical history of undergoing vitrectomy for
Dr. Arthur D. Fu (San Francisco, California): The authors present a 23-year-old-man with a history of RD and proliferative vitreoretinopathy in one eye and subsequently developed RD in the fellow eye, successfully repaired with vitrectomy and gas fluid exchange. Intraoperatively, the authors noted vitreous liquefaction and a posterior vitreous detachment suspicious for one at such a young age. Subsequently, FAF demonstrated a ring of hyperautofluorescence, a peculiar granular hypoautofluorescence along the vascular arcades, and severe depression in both rod and cone functions in the repaired fellow eye. We are asked to consider possible diagnoses and to hypothesize the etiology of the autofluorescence patterns. A history of bilateral RD at a relatively young age in concert with prematurely liquified vitreous prompts consideration of inherited RD disorders. Patients with very high myopia are certainly at risk for early syneresis and liquefaction of their vitreous, but a posterior vitreous detachment at a young age is less common. The differential of inherited vitreoretinal degeneration includes Wagner syndrome, erosive vitreoretinopathy (ERVR), Jansen syndrome, Stickler 2153
2154 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
2014 VOLUME 34 NUMBER 10
Fig. 1. Ultrawide-field fundus photographs (A and C) and FAF images (B and D) at the initial visit. A and B. Right eye images. C and D. Left eye images. The white arrows in (C) point to the original retinal tears.
syndrome, snowflake degeneration, Goldmann–Favre syndrome, and Knobloch syndrome. Wagner syndrome, ERVR, and Jansen syndrome are collectively known as 5q retinopathies as they have been localized to the same chromosome and are inherited in an autosomal dominant pattern.4,5 Wagner syndrome is described as an entity that is characterized by an optically empty vitreous with avascular vitreous strands and veils, moderate myopia, presenile cataracts, and retinal degeneration with atrophy. Erosive vitreoretinopathy shares features with Wagner syndrome, including the nyctalopia, constriction of visual fields, chorioretinal atrophy, and propensity for RRD.5 It is important to note that both Wagner syndrome and
Fig. 2. Ultrawide-field fundus photograph (A) and fundus autofluorescence (B) image one month after a vitrectomy for rhegmatogenous retinal detachment in the left eye. The temporal pigmentation is a scar of the endolaser photocoagulation.
ERVR may have electroretinographic abnormalities of both rod and cone functions, but are typically not extinguished. Snowflake vitreoretinal degeneration is not on the 5q chromosome, but shares abnormalities of vitreous and reported risk of RD.6 Characteristic small yellow white deposits in the periphery seen in patients with snowflake vitreoretinal degeneration were not described in our patient. Knobloch syndrome clinical features include smooth (cryptless) irides, high myopia, and vitreoretinal degeneration consisting of diffuse retinal pigment epithelium atrophy with prominent choroidal vessel show, macular atrophic lesions with or without a “punched out” appearance, and white fibrillar
DIAGNOSTIC AND THERAPEUTIC CHALLENGES
2155
Fig. 3. Full-field ERGs recorded 1 month after the vitrectomy for RRD in the left eye. A. Scotopic ERG. B. Flash ERG. C. Photopic ERG. D. 30-Hz flicker ERG.
vitreous condensations. Systemic features of this autosomal recessive disease include occipital encephalocele. Retinal detachment is a known feature of Knobloch syndrome. Rhegmatogenous retinal detachment in patients with RP (rod or rod–cone dystrophy) is a rare event.7 Case series are limited and associated risk factors include young age and the presence of myopia.7–10 In these younger patients, a common finding is sine pigmenti, or the lack of intraretinal pigment migration or underlying retinal pigment epithelial alteration. It has been hypothesized that adhesions between retinal pigment epithelium and neurosensory retina histologically seen in advanced cases of RP may not be present in younger patients with less severe disease.7 Therefore, younger patients with RP may have no additional protection against RD. Bilateral detachments secondary to giant retina tears in one case series were documented in patients with sensorineural hearing loss, some with clinical features of Usher Syndrome.11,12 In these rare cases, the diagnosis of the RRD preceded the eventual diagnosis of RP. What do the combination of severely depressed ERGs and FAF patterns tell us? Fundus autofluorescence has certainly emerged as an exciting method in characterizing retinal conditions. In RP, a ring of high-density hyperautofluorescence around the fovea indicates a transition from high concentrations of lipofuscin and other fluorophores surrounding more normal central macular retina and retinal pigment epithelium.13–16 Although most commonly described in RP, these parafoveal hyperautofluorescent rings may not be specific to RP. With any relatively new imaging
modality, other entities may yet prove to have a ring of hyperautofluorescence, and published reports of hyperautofluorescent rings are also noted in autoimmune retinopathy. Double hyperautofluorescent rings are noted in Goldmann–Favre syndrome from mutations in the NR2E3 gene.17 Goldmann–Favre syndrome, also thought to be synonymous with enhanced S-cone syndrome, would be a prime candidate. However, a key feature in this disease is an electrophysiologic finding in which photopic and scotopic waveforms are similar, rod-specific function is extremely depressed, and 30-Hz flicker implicit time is delayed. This is seen because of residual S-cone short wavelength activity. However, there is wide phenotypic variability, both in electrophysiologic and clinical findings in patients with NR2E3 mutations. In this patient, the severely depressed rod and cone functions without the finding of similar photopic and scotopic waveforms make it difficult to confirm whether this patient has a form of Goldmann–Favre syndrome. An extensive PubMed review of FAF of Wagner disease and other aforementioned vitreoretinal degenerative syndromes yielded no reports of hyperautofluorescent rings. The hypoautofluorescent areas in a paramacular distribution are also described in patients with RP. Using wide-field FAF, Oishi et al18 characterized hypoautofluorescence in a spectrum corresponding to severity of disease. Smaller, granular, or reticular areas of hypoautofluorescence similar to those seen in our young patient were seen in less severe stages of RP. As the severity increased, patients often developed larger areas of patchy hypoautofluorescence corresponding to visual field deficits. Other forms of
2156 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
2014 VOLUME 34 NUMBER 10
Fig. 4. Goldmann perimetry performed 1 month after the vitrectomy for the RRD in the left eye. The result of perimetry for the left eye is shown on the left side.
“patchy” hypoautofluorescence have been described in choroideremia.19 The combination of severely depressed rod and cone functions on ERG, hyperautofluorescent parafoveal ring, and granular hypoautofluorescent areas suggests an unfortunate patient with RP or Goldmann–Favre syndrome who also was unlucky enough to have bilateral RD. Consideration for genetic testing for the multiple genes associated with RP and NR2E3 mutations should be considered. The nearly undetectable rod function ERGs make vitreoretinal degenerative disorders such as ERVR less likely. However, a careful family history and systemic examination to confirm the presence of any syndromic vitreoretinal degenerative disorders such as Sticklers syndrome, Wagner syndrome, and Knobloch syndrome are advised. Additional genetic testing for 5q chromosomal abnormalities may be necessary to rule out the remote possibility that these conditions also have hyperautofluorescent parafoveal rings and granular hypoautofluorescent rings. Editor’s Note: Drs. Sato and Emi have presented a 23-year-old man with a superior bullous RD in 1 eye and a history of surgery for proliferative vitreoretinopathy 10 years earlier in his other eye. The retina was reattached with good visual recovery, but the FAF revealed unusual macular findings, visual field defects, and reduced ERGs in each eye. The case is presented for discussion of diagnosis, analysis of the autofluorescent findings, and management. Dr. Fu has agreed to consult on this case and addresses the issue of RD at a young age. He notes that
consideration be given to inherited disorders and offers the following differential diagnosis: I. Wagner syndrome II. Erosive vitreoretinopathy III. Jansen syndrome IV. Stickler syndrome V. Snowflake degeneration VI. Goldman–Favre syndrome VII. Knobloch syndrome
He reviews these entities and emphasizes that both Wagner syndrome and ERVR may have abnormalities of both rod and cone functions, but are typically not extinguished. Together these 2 diagnoses, along with Jansen syndrome are known as 5q retinopathies as they are localized to the same chromosome and inherited in an autosomal pattern. Dr. Fu examines the possibility that this patient had RP and states that a lack of intraretinal pigment migration, sine pigmenti, is a common finding in younger patients. Furthermore, he notes the speculation that adhesions between the RPE and neurosensory retina may not be present in younger patients with less severe disease because they are in advanced cases of RP. He addresses the issue of fundus autofluorescent findings. He states that in RP, a ring of high density hyperautofluorescence around the fovea indicates a transition from high concentration of lipofuscin and other fluorophores surrounding more central macular retina and RPE. Similar rings of hyperautofluorescence are noted in Goldman–Favre syndrome from mutations in the NR2E3 gene. Similarly, the paramacular hypoautofluorescent areas are seen in RP. He believes that granular areas of hypoautofluorescence in this young patient are consistent with the reports of less severe stages of RP.
DIAGNOSTIC AND THERAPEUTIC CHALLENGES
Dr. Fu concludes that this patient with bilateral RD has RP and suggests testing for multiple genes associated with RP. He advocates for additional testing for 5q chromosomal abnormalities and for a careful family history and systemic evaluation. We thank Drs. Sato and Emi for their case and Dr. Fu for his consultation. References 1. Robson AG, El-Amir A, Bailey C, et al. Pattern ERG correlates of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity. Invest Ophthalmol Vis Sci 2003;44:3544–3550. 2. Popovic P, Jarc-Vidmar M, Hawlina M. Abnormal fundus autofluorescence in relation to retinal function in patients with retinitis pigmentosa. Graefes Arch Clin Exp Ophthalmol 2005; 243:1018–1027. 3. Murakami T, Akimoto M, Ooto S, et al. Association between abnormal autofluorescence and photoreceptor disorganization in retinitis pigmentosa. Am J Ophthalmol 2008;145:687–694. 4. Miyamoto T, Inoue H, Sakamoto Y, et al. Identification of a novel splice site mutation of the CSPG2 gene in a Japanese family with Wagner syndrome. Invest Ophthalmol Vis Sci 2005;46:2726–2735. 5. Brown DM, Kimura AE, Weingeist TA, Stone EM. Erosive vitreoretinopathy. A new clinical entity. Ophthalmology 1994; 101:694–704. 6. Jiao X, Ritter R III, Hejtmancik JF, Edwards AO. Genetic linkage of snowflake vitreoretinal degeneration to chromosome 2q36. Invest Ophthalmol Vis Sci 2004;45:4498–4503. 7. Edwards RS, Calder IG, Crews SJ. Retinal detachment in retinitis pigmentosa. Trans Ophthalmol Soc U K 1985;104:315–318. 8. Johnston GP. Retinitis pigmentosa and retinal detachment. A case report. Retina 1981;1:223–226. 9. Demir MN, Unlu N, Yalniz Z, et al. A case of retinal detachment in retinitis pigmentosa. Eur J Ophthalmol 2007;17: 677–679. 10. Lee SY, Ong SG. Ring retinal detachment in retinitis pigmentosa. Arch Ophthalmol 2006;124:1794.
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11. Kim RY, Schwartz SD, Heckenlively JR, et al. Giant retinal tear and retinal detachment with underlying retinitis pigmentosa and hearing loss. Eye (Lond) 1996;10:697–700. 12. Johnston ME, Gonder JR. Giant retinal tears, retinal detachment and retinitis pigmentosa. Can J Ophthalmol 1985;20:16–18. 13. Robson AG, Egan C, Holder GE, et al. Comparing rod and cone function with fundus autofluorescence images in retinitis pigmentosa. Adv Exp Med Biol 2003;533:41–47. 14. Robson AG, El-Amir A, Bailey C, et al. Pattern ERG correlates of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity. Invest Ophthalmol Vis Sci 2003;44:3544–3550. 15. Robson AG, Saihan Z, Jenkins SA, et al. Functional characterisation and serial imaging of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity. Br J Ophthalmol 2006;90:472–479. 16. Robson AG, Tufail A, Fitzke F, et al. Serial imaging and structure-function correlates of high-density rings of fundus autofluorescence in retinitis pigmentosa. Retina 2011;31:1670–1679. 17. Escher P, Tran HV, Vaclavik V, et al. Double concentric autofluorescence ring in NR2E3-p.G56R-linked autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci 2012;53:4754–4764. 18. Oishi A, Ogino K, Makiyama Y, et al. Wide-field fundus autofluorescence imaging of retinitis pigmentosa. Ophthalmology. 2013;120:1827–1834. 19. Yuan A, Kaines A, Jain A, et al. Ultra-wide-field and autofluorescence imaging of choroidal dystrophies. Ophthalmic Surg Lasers Imaging 2010;41:e1–e5.
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.
