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Purpose: To identify specific mutations causing North Carolina macular dystrophy (NCMD)., Design: Whole-genome sequencing coupled with reverse transcription polymerase chain reaction (RT-PCR) analysis of gene expression in human retinal cells., Participants: A total of 141 members of 12 families with NCMD and 261 unrelated control individuals., Methods: Genome sequencing was performed on 8 affected individuals from 3 families affected with chromosome 6-linked NCMD (MCDR1) and 2 individuals affected with chromosome 5-linked NCMD (MCDR3). Variants observed in the MCDR1 locus with frequencies <1% in published databases were confirmed using Sanger sequencing. Confirmed variants absent from all published databases were sought in 8 additional MCDR1 families and 261 controls. The RT-PCR analysis of selected genes was performed in stem cell-derived human retinal cells., Main Outcome Measures: Co-segregation of rare genetic variants with disease phenotype., Results: Five sequenced individuals with MCDR1-linked NCMD shared a haplotype of 14 rare variants spanning 1 Mb of the disease-causing allele. One of these variants (V1) was absent from all published databases and all 261 controls, but was found in 5 additional NCMD kindreds. This variant lies in a DNase 1 hypersensitivity site (DHS) upstream of both the PRDM13 and CCNC genes. Sanger sequencing of 1 kb centered on V1 was performed in the remaining 4 NCMD probands, and 2 additional novel single nucleotide variants (V2 in 3 families and V3 in 1 family) were identified in the DHS within 134 bp of the location of V1. A complete duplication of the PRDM13 gene was also discovered in a single family (V4). The RT-PCR analysis of PRDM13 expression in developing retinal cells revealed marked developmental regulation. Next-generation sequencing of 2 individuals with MCDR3-linked NCMD revealed a 900-kb duplication that included the entire IRX1 gene (V5). The 5 mutations V1 to V5 segregated perfectly in the 102 affected and 39 unaffected members of the 12 NCMD families., Conclusions: We identified 5 rare mutations, each capable of arresting human macular development. Four of these strongly implicate the involvement of PRDM13 in macular development, whereas the pathophysiologic mechanism of the fifth remains unknown but may involve the developmental dysregulation of IRX1., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Unlabelled: RETINAL VEIN OCCLUSIONS PREFERRED PRACTICE PATTERN®, Guidelines: New evidence-based Retinal Vein Occlusions Preferred Practice Pattern® (PPP) guidelines, discussing the prognosis and risk factors of retinal vein occlusions and the treatment options., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Unlabelled: IDIOPATHIC EPIRETINAL MEMBRANE AND VITREOMACULAR TRACTION PREFERRED PRACTICE PATTERN®, Guidelines: New evidence-based Idiopathic Epiretinal Membrane and Vitreomacular Traction Preferred Practice Pattern® (PPP) guidelines, describing recommendations for the diagnosis, treatment, and management of patients., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the outcomes of combination anti-vascular endothelial growth factor (VEGF) and photodynamic therapy (PDT) for the treatment of neovascular age-related macular degeneration (AMD) refractory to anti-VEGF monotherapy., Design: Retrospective, interventional case series., Participants: Twenty-six eyes of 26 patients treated with anti-VEGF monotherapy for neovascular AMD with persistent subretinal or intraretinal fluid after at least 3 anti-VEGF injections in the 7 months before combination treatment., Intervention: Combination anti-VEGF treatment and PDT., Main Outcome Measures: Visual acuity at 1 or 2, 3, and 6 months and central retinal thickness at 1 or 2, 3, and 6 months. Secondary outcome measures were change in number of fluid-free visits and interval between treatments in the 7 months before and 6 months after combination therapy., Results: Statistically significant improvements in logarithm of the minimum angle of resolution visual acuities were present at 1 month (P = 0.01) and 3 months (P = 0.01). Significant decreases in central subfield retinal thickness on optic coherence tomography (OCT) were seen at 1 month (P = 4×10(-5)), 3 months (P = 3×10(-4)), and 6 months (P = 4×10(-5)) as compared with precombination treatment OCT scans. The percentage of patient visits with no subretinal fluid increased from 0.5% to 41% after the initiation of combination therapy (P = 1×10(-5)). The interval between treatments increased from once every 1.6 months in the 7 months before combination treatment to once every 2.7 months in the 6 months after combination treatment (P = 0.002). No ocular complications attributable to PDT were seen., Conclusions: Rescue therapy with the combination of anti-VEGF and PDT in eyes that have failed anti-VEGF monotherapy resulted in a mean improvement in vision, a decreased central subfield retinal thickness, and an increase in fluid-free intervals., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine whether vitrectomy alters the long-term progression of age-related macular degeneration (AMD)., Design: Retrospective case-control study., Participants: Forty-four eyes of 22 patients with AMD who underwent vitrectomy in 1 eye were included in the study. The progression of AMD at follow-up in the 22 eyes that underwent vitrectomy was compared with the 22 fellow, nonvitrectomized eyes., Methods: The charts and photographs of subjects with Age-Related Eye Disease Study category 3 AMD in both eyes who previously underwent vitrectomy surgery for an epiretinal membrane or macular hole were reviewed. Subjects were excluded if they had had a vitrectomy in both eyes, had <2 years of follow-up, had previous choroidal neovascularization (CNV), retinal detachment, diabetic retinopathy, angioid streaks, high myopia, vascular occlusions, or extensive macular scarring in either eye, or insufficient hospital records or photographs to determine the extent of AMD. Clinical notes throughout the follow-up interval were reviewed. Two vitreoretinal specialists independently graded pre- and postvitrectomy fundus photographs of all eyes in a masked fashion., Main Outcome Measures: The development or progression of geographic atrophy of the retinal pigment epithelium and the development of CNV., Results: Twenty-two patients were included. The average follow up interval was 5.5 years (range, 2-15). Choroidal neovascularization developed in 5 control eyes and in 2 vitrectomized eyes, and atrophy developed in 7 control and 4 vitrectomized eyes. The difference between vitrectomized eyes and fellow eyes for the combined end points of RPE geographic atrophy or CNV was significant (P = 0.02)., Conclusions: In this pilot study, we did not detect that vitrectomy increased the progression of AMD. In fact, it was associated with a reduced progression to geographic atrophy or CNV. Additional studies are needed to confirm or refute this association., Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the performance of automated diabetic retinopathy (DR) detection, using the algorithm that won the 2009 Retinopathy Online Challenge Competition in 2009, the Challenge2009, against that of the one currently used in EyeCheck, a large computer-aided early DR detection project., Design: Evaluation of diagnostic test or technology., Participants: Fundus photographic sets, consisting of 2 fundus images from each eye, were evaluated from 16670 patient visits of 16,670 people with diabetes who had not previously been diagnosed with DR., Methods: The fundus photographic set from each visit was analyzed by a single retinal expert; 793 of the 16,670 sets were classified as containing more than minimal DR (threshold for referral). The outcomes of the 2 algorithmic detectors were applied separately to the dataset and were compared by standard statistical measures., Main Outcome Measures: The area under the receiver operating characteristic curve (AUC), a measure of the sensitivity and specificity of DR detection., Results: Agreement was high, and examination results indicating more than minimal DR were detected with an AUC of 0.839 by the EyeCheck algorithm and an AUC of 0.821 for the Challenge2009 algorithm, a statistically nonsignificant difference (z-score, 1.91). If either of the algorithms detected DR in combination, the AUC for detection was 0.86, the same as the theoretically expected maximum. At 90% sensitivity, the specificity of the EyeCheck algorithm was 47.7% and that of the Challenge2009 algorithm was 43.6%., Conclusions: Diabetic retinopathy detection algorithms seem to be maturing, and further improvements in detection performance cannot be differentiated from best clinical practices, because the performance of competitive algorithm development now has reached the human intrareader variability limit. Additional validation studies on larger, well-defined, but more diverse populations of patients with diabetes are needed urgently, anticipating cost-effective early detection of DR in millions of people with diabetes to triage those patients who need further care at a time when they have early rather than advanced DR., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: We examined whether implantation of the fluocinolone acetonide (Retisert) implant achieved control of inflammation and a reduced need for oral corticosteroids or immunosuppressives in patients with sympathetic ophthalmia (SO)., Design: Retrospective, noncomparative case series., Participants: Eight patients with active SO., Methods: The results of fluocinolone acetonide implantation in 8 patients with active SO were studied with a follow-up period of 6 months to 2 years., Main Outcome Measures: Presence or absence of intraocular inflammation, visual acuity, intraocular pressure, need for further surgery, and the need for additional use of oral or locally injected corticosteroids and/or immunosuppressives., Results: All patients demonstrated a significant reduction in the systemic medication required to maintain control of inflammation. Two patients had recurrent inflammatory episodes requiring the resumption of an oral immunosuppressive. Vision improved or was stabilized in all 8 patients., Conclusions: The fluocinolone acetonide implant provides inflammatory control and reduces the dependence on systemic immunosuppression in patients with SO.