A 32 kb Critical Region Excluding Y402H in CFH Mediates Risk for Age-Related Macular Degeneration

Complement factor H shows very strong association with Age-related Macular Degeneration (AMD), and recent data suggest that multiple causal variants are associated with disease. To refine the location of the disease associated variants, we characterized in detail the structural variation at CFH and its paralogs, including two copy number polymorphisms (CNP), CNP147 and CNP148, and several rare deletions and duplications. Examination of 34 AMD-enriched extended families (N = 293) and AMD cases (White N = 4210 Indian = 134; Malay = 140) and controls (White N = 3229; Indian = 117; Malay = 2390) demonstrated that deletion CNP148 was protective against AMD, independent of SNPs at CFH. Regression analysis of seven common haplotypes showed three haplotypes, H1, H6 and H7, as conferring risk for AMD development. Being the most common haplotype H1 confers the greatest risk by increasing the odds of AMD by 2.75-fold (95% CI = [2.51, 3.01]; p = 8.31×10−109); Caucasian (H6) and Indian-specific (H7) recombinant haplotypes increase the odds of AMD by 1.85-fold (p = 3.52×10−9) and by 15.57-fold (P = 0.007), respectively. We identified a 32-kb region downstream of Y402H (rs1061170), shared by all three risk haplotypes, suggesting that this region may be critical for AMD development. Further analysis showed that two SNPs within the 32 kb block, rs1329428 and rs203687, optimally explain disease association. rs1329428 resides in 20 kb unique sequence block, but rs203687 resides in a 12 kb block that is 89% similar to a noncoding region contained in ΔCNP148. We conclude that causal variation in this region potentially encompasses both regulatory effects at single markers and copy number

Retinal vasculitis associated with CREST syndrome

Purpose: To report two cases of retinal vasculitis associated with CREST syndrome, a novel ocular finding. Observations: We report two cases of patients with CREST syndrome with ocular inflammatory disease. Patient 1 presented with a right unilateral panuveitis with extensive retinal vasculitis and evidence of prior uveitis in the contralateral eye. Patient 2 presented with a left branch retinal artery occlusion and bilateral retinal vasculitis. Both patients underwent treatment with prednisone and mycophenolate motefil. Conclusions and importance: Retinal vasculitis has not been previously reported in CREST syndrome. Prompt therapy with immunomodulatory therapy can potentially minimize ocular morbidity. Keywords: CREST syndrome, Retinal vasculiti

Uveitis reactivation following recombinant zoster vaccination

Purpose: Describe three cases of uveitis reactivation following immunization with recombinant zoster vaccine (RZV). Observations: One patient developed reactivation of previously controlled multifocal choroiditis within one week of receiving RZV, requiring treatment with systemic corticosteroids. Two patients with previously controlled anterior uveitis developed new anterior segment inflammation after RZV; both were treated with topical corticosteroids and systemic antiviral therapy. Conclusion and importance: Uveitis recurrence is an infrequent but serious potential ocular side effect of recombinant zoster vaccination

Pathological Findings of Synchysis Scintillans Secondary to Familial Exudative Vitreoretinopathy With Chronic Exudative Retinal Detachment

Purpose: We describe a unique case of synchysis scintillans in a 23-year-old woman with a history of chronic exudative retinal detachment in the setting of familial exudative vitreoretinopathy. Methods: Fundus and slit-lamp photographs were obtained at presentation, and pathological studies were performed on the enucleated specimen to confirm the diagnosis. Results: Synchysis scintillans is a degenerative condition of cholesterol deposition that affects severely damaged eyes, often as a result of chronic vitreous hemorrhage or retinal detachment. In this case, synchysis scintillans presented as crystals in the anterior chamber in the setting of a chronic retinal detachment. After enucleation, there were noted to be cholesterol slits on pathological correlation, confirming the diagnosis. Conclusions: This case demonstrates the importance of clinical pathological correlation in the diagnosis of synchysis scintillans migrating into the anterior chamber

Recovery of outer retinal laminations on optical coherence tomography after treatment of cancer associated retinopathy

Purpose: To report novel optical coherence tomography findings in a case of anti-α-enolase cancer associated retinopathy. Observations: An elderly female presented with bilateral decreased vision and a recent diagnosis of ovarian carcinoma. Optical coherence tomography demonstrated bilateral loss of outer retinal structures and macular edema. Serum testing found antibodies against α-enolase and 82–84 kDa proteins. Outer retinal structures showed recovery, macular edema resolved and repeat anti-retinal antibody testing became negative following cancer therapy and topical difluprednate treatment. Conclusions and importance: Cancer associated retinopathy is a paraneoplastic disease that results in damage to retinal structures through an autoimmune response. The damage is generally considered to be irreversible; however, in rare cases, such as observed here, retinal structures may demonstrate recovery after treatment