JAMA Ophthalmology Online First

Phenotypic Conservation in Patients With X-Linked Retinitis Pigmentosa Caused by RPGR Mutations Phenotypic Conservation in Patients With XLRP

Zahid S, Khan N, Branham K, et al. — Thu, 16 May 2013 00:00:00 GMT

Importance

For patients with X-linked retinitis pigmentosa and clinicians alike, phenotypic variability can be challenging because it complicates counseling regarding patients' likely visual prognosis.

Objective

To evaluate the clinical findings from patients with X-linked retinitis pigmentosa with 13 distinct RPGR mutations and assess for phenotypic concordance or variability.

Design

Retrospective medical record review of data collected from 1985 to 2011.

Setting

Kellogg Eye Center, University of Michigan.

Patients

A total of 42 patients with X-linked retinitis pigmentosa with mutations in RPGR. Age at first visit ranged from 4 to 53 years, with follow-up ranging from 1 to 11 visits (median follow-up time, 5.5 years; range, 1.4-32.7 years, for 23 patients with >1 visit).

Main Outcomes and Measures

Clinical data assessed for concordance included visual acuity (VA), Goldmann visual fields (GVFs), and full-field electroretinography (ERG). Electroretinography phenotype (cone-rod vs rod-cone dysfunction) was defined by the extent of photopic vs scotopic abnormality. Qualitative GVF phenotype was determined by the GVF pattern, where central or peripheral loss suggested cone or rod dysfunction, respectively. Goldmann visual fields were also quantified and compared among patients.

Results

Each mutation was detected in 2 or more related or unrelated patients. Five mutations in 11 patients displayed strong concordance of VA, while 4 mutations in 16 patients revealed moderate concordance of VA. A definitive cone-rod or rod-cone ERG pattern consistent among patients was found in 6 of 13 mutations (46.2%); the remaining mutations were characterized by patients demonstrating both phenotypes or who had limited data or nonrecordable ERG values. Concordant GVF phenotypes (7 rod-cone pattern vs 4 cone-rod pattern) were seen in 11 of 13 mutations (84.6%). All 6 mutations displaying a constant ERG pattern within the mutation group revealed a GVF phenotype consistent with the ERG findings.

Conclusions and Relevance

While VA and ERG phenotypes are concordant in only some patients carrying identical mutations, assessment of GVF phenotypes revealed stronger phenotypic conservation. Phenotypic concordance is important for establishing proper counseling of patients diagnosed as having X-linked retinitis pigmentosa, as well as for establishing accurate patient selection and efficacy monitoring in therapeutic trials.

Association of Ocular and Oculodermal Melanocytosis With the Rate of Uveal Melanoma Metastasis Analysis of 7872 Consecutive Eyes Oculo(dermal) Melanocytosis and Uveal Melanoma

Shields CL, Kaliki S, Livesey M, et al. — Thu, 16 May 2013 00:00:00 GMT

Importance

Ocular/oculodermal (oculo[dermal]) melanocytosis is a congenital periocular pigmentary condition that can lead to the development of uveal melanoma, estimated at 1 in 400 affected patients. In this study, patients with melanocytosis who developed uveal melanoma were found to have double the risk for metastasis compared with those without melanocytosis.

Objective

To determine the relationship of oculo(dermal) melanocytosis to the prognosis of patients with uveal melanoma.

Design, Setting, and Patients

Retrospective chart review of 7872 patients with uveal melanoma treated at the Ocular Oncology Service, Wills Eye Institute, from August 25, 1970, through August 27, 2008.

Exposures

Enucleation, plaque radiotherapy, local resection, or thermotherapy.

Main Outcomes and Measures

Metastasis and death.

Results

Of 7872 patients with uveal melanoma, oculo(dermal) melanocytosis was present in 230 (3%). The melanocytosis involved the sclera (92%), iris (17%), choroid (12%), eyelid (8%), and temporal fossa (1%). Eyes with melanoma and oculo(dermal) melanocytosis had a relative risk for metastasis 1.6 times greater compared with those with no melanocytosis (P < .001). Metastasis of uveal melanoma was 2.8 times higher in patients with iris melanocytosis (P < .001), 2.6 times higher with choroidal melanocytosis (P = .02), and 1.9 times higher with scleral melanocytosis (P < .001). By Kaplan-Meier estimates, metastasis in patients with oculo(dermal) melanocytosis vs no melanocytosis was 2% vs 1.8% at 1 year, 27% vs 15% at 5 years, and 48% vs 24% at 10 years (P < .001). By multivariable analysis, the factors predictive of metastasis in patients harboring uveal melanoma associated with oculo(dermal) melanocytosis were increased tumor thickness (P = .001) and the presence of subretinal fluid (P = .05), and the only factor predictive of death was increased tumor thickness (P = .009).

Conclusions and Relevance

Patients with uveal melanoma associated with oculo(dermal) melanocytosis have double the risk for metastasis compared with those with no melanocytosis. All patients with oculo(dermal) melanocytosis should undergo ophthalmic examination and imaging on a twice-yearly basis because this could help with the early detection of melanoma.

Intrachoroidal Cavitation in North Carolina Macular Dystrophy

Schoenberger SD, Agarwal A. — Thu, 16 May 2013 00:00:00 GMT

North Carolina macular dystrophy (NCMD) is an autosomal dominantly inherited condition with 3 phenotypic grades. Grade 1 has yellow or white drusenlike deposits. Grade 2 features confluent drusen, pigmentary changes, retinal pigment epithelial (RPE) atrophy, or subretinal scarring. Grade 3 is described as a macular staphyloma, coloboma, or caldera with hyperpigmentation and subretinal fibrosis. Different grades and expressivity may be seen within one family, and the etiology is unknown.

A Novel Technique of Modified Continuous Blanket Suture for Amniotic Membrane Fixation in Severe Ocular Surface Diseases Modified Continuous Blanket Suture

Zhang Z, Ma H, Chen D, et al. — Thu, 16 May 2013 00:00:00 GMT

The purpose of this article is to demonstrate a novel technique using modified continuous blanket suture (MCBS) to fix the amniotic membrane (AM) in different severe ocular surface disease lesions. The MCBS techniques were used to fix the AMs of 5 representative patients with different ocular surface lesions related to severe ocular surface diseases. In all cases, stable adherence of the AM was maintained until the epithelialization of the ocular surface was completed. No early detachment, dissolution, or dislocation of the AM patch was observed. During follow-up, all patients acquired a smooth and acceptable ocular surface without any persistent epithelial defect, infection, or ulceration. The MCBS method achieved good AM fixation on the ocular surface in cases of severe ocular surface lesions and could prevent the early detachment of the AM and promote the epithelialization of the ocular surface.

Paul A. Cibis, MD A Pioneer of Modern Vitreoretinal Surgery Paul A. Cibis, MD

Feibel RM, Blodi CF. — Thu, 16 May 2013 00:00:00 GMT

Paul Anton Cibis (1911-1965) was one of the pioneers of modern vitreoretinal surgery. He reasoned that the pathology of complex retinal detachments was intravitreal fibrosis and concluded that the optimum surgery was the injection of liquid silicone oil into the vitreous cavity to dissect fibrous membranes from the retinal surface and use the silicone for retinal tamponade. Prior to the invention of pars plana vitrectomy, such surgery was innovative, even daring. These surgical techniques were an important advance in directly operating on the vitreous in retinal detachment surgery. However, Cibis' contributions to vitreoretinal surgery only occupied the last 10 years of his tragically short life. Prior to his practice in retinal surgery, he made contributions to basic research in physiologic optics, local retinal adaptation, and the effect of ionizing radiation and atomic energy on the globe.