Antonio Capone

Lens-sparing vitreous surgery for tractional stage 4A retinopathy of prematurity retinal detachments

PURPOSE To assess the efficacy of lens-sparing vitrectomy in tractional 4A retinopathy of prematurity (ROP) retinal detachments in reducing progression to stage 4B or 5 ROP. DESIGN Retrospective, noncomparative consecutive case series. PARTICIPANTS Forty eyes (31 patients) with stage 4A ROP at 38 to 42 weeks post-conceptional age. INTERVENTION Lens-sparing vitrectomy. MAIN OUTCOME MEASURES Retinal attachment status and presence/absence of fixation behavior. RESULTS The range of follow-up was 6 to 22 months (mean, 12 months). Ninety percent (36 of 40) of eyes showed retinal reattachment and fixation behavior at their last follow-up visit. CONCLUSIONS These results suggest that vitreous surgery can interrupt progression of ROP from stage 4A to stages 4B or 5.

Outcome of Eyes Developing Retinal Detachment During the Early Treatment for Retinopathy of Prematurity Study (ETROP)

OBJECTIVE To describe the structural and visual outcomes at age 6 years of retinal detachment (RD) from retinopathy of prematurity (ROP) in the Early Treatment for Retinopathy of Prematurity (ETROP) study. METHODS Prospective multicenter nonrandomized series of infants with high-risk prethreshold ROP who developed an RD by 6 months corrected age treated with observation or vitreoretinal surgery. RESULTS Of 401 patients, 63 (89 eyes) experienced RD. Follow-up at age 6 years was available for 70 eyes (79%) of 49 surviving patients. The RDs were stage 4A in 28 eyes (40%), stage 4B in 14 (20%), stage 5 in 13 (19%), and not classified in 15 (21%). The macula was attached in 17 of 50 eyes (34%) after vitrectomy with or without scleral buckle, in 6 of 9 (67%) after scleral buckle only, and in 2 of 11 eyes (18%) observed. An attached macula at age 6 years after vitreoretinal surgery was present in 5 of 16 eyes (31%) with stage 4A, 6 of 10 (60%) with stage 4B, and 0 of 10 with stage 5. Favorable visual acuity (>20/200) was found in 6 of 70 eyes (9%); 5 had stage 4A, and 1 was not classified. CONCLUSIONS Macular attachment was achieved in approximately one-third of eyes with RD and favorable visual acuity in some eyes with stage 4A.

Alleles in the HtrA Serine Peptidase 1 Gene Alter the Risk of Neovascular Age-Related Macular Degeneration

OBJECTIVE To examine if the genes encoding the pleckstrin homology domain-containing protein gene (PLEKHA1), hypothetical LOC387715/ARMS2 gene, and HtrA serine peptidase 1 gene (HTRA1) located on the long arm of chromosome 10 (10q26 region) confer risk for neovascular age-related macular degeneration (AMD) in an independent or interactive manner when controlling for complement factor H gene (CFH) genotype and smoking exposure. DESIGN Retrospective matched-pair case-control study. PARTICIPANTS Hospital clinic-based sample of 134 unrelated patients with neovascular AMD who have a sibling with normal maculae (268 subjects). METHODS Disease status was ascertained by at least 2 investigators by review of fundus photographs and/or fluorescein angiography according to the Age-Related Eye Disease Study grading scale. If necessary, a home retinal examination was performed (n = 6). A combination of direct sequencing and analysis of 8 highly polymorphic microsatellite markers was used to genotype 33 megabases of the 10q26 region on leukocyte DNA. Smoking history was obtained via a standardized questionnaire and measured in pack-years. The family-based association test, haplotype analysis, multiple conditional logistic regression, and linkage analysis were used to determine significant associations. MAIN OUTCOME MEASURE Neovascular AMD status. RESULTS Of the 23 variants we identified in the 10q26 region, 6 were significant. Four of the 6 were novel and included 2 genotypes that reduced risk of AMD. Many single-nucleotide polymorphisms (SNPs), including the previously reported variants rs10490924 (hypothetical LOC387715/ARMS2) and rs11200638 (HTRA1), defined 2 significant haplotypes associated with increased risk of neovascular AMD. The coding HTRA1 SNP rs2293870, not part of the significant haplotypes containing rs10490924 and rs11200638, showed as strong an association with increased susceptibility to neovascular AMD. Linkage analysis supported our findings of SNP association (P<10(-15)). No significant interactions were found between any of the SNPs in the 10q26 and smoking or between these SNPs and CFH genotype. CONCLUSIONS Independent of CFH genotype or smoking history, an individuals risk of AMD could be increased or decreased, depending on their genotype or haplotype in the 10q26 region.

Incidence of retinal detachment and visual outcome in eyes presenting with posterior vitreous separation and dense fundus-obscuring vitreous hemorrhage

PURPOSE To determine visual outcomes and the incidence of retinal detachment in eyes presenting with posterior vitreous separation and dense fundus-obscuring vitreous hemorrhage. DESIGN Retrospective consecutive noncomparative interventional case series. PARTICIPANTS Thirty-six eyes (15 right eyes and 21 left eyes) of 34 patients (18 female and 16 male) ranging in age from 42 to 94 years. Mean follow-up was 14 months. METHODS A comparison of the best-corrected initial visual acuities versus final visual acuities after spontaneous resolution of vitreous hemorrhage or surgical intervention. The number of eyes that were found to have retinal tears or that had a rhegmatogenous retinal detachment develop was documented. Logarithm of the minimum angle of resolution-converted visual acuities was used for comparison. Categorical data were analyzed by Fishers exact test, and population means were compared by Students t test. MAIN OUTCOME MEASURES Final mean visual acuities, number of eyes with at least one retinal tear, location of retinal tears, number of eyes that had retinal detachment develop, and the number of eyes repaired with scleral buckling surgery and/or pars plana vitrectomy. RESULTS Twenty-four of 36 eyes (67%) were found to have at least one retinal break (range, 0-4 breaks), with 88% of breaks located in the superior retina. Eleven eyes (31%) had more than one retinal break. Fourteen of 36 eyes (39%) had a rhegmatogenous retinal detachment develop that was repaired with pars plana vitrectomy and scleral buckling. An additional 14 eyes (39%) underwent vitrectomy for nonclearing vitreous hemorrhage. The incidence of retinal detachment in eyes with a history of retinal detachment in the contralateral eye was 75% (P = 0.04). Seven of 14 eyes (50%) with retinal detachment had coexisting proliferative vitreoretinopathy. Most retinal breaks and detachments occurred in emmetropic or myopic eyes. For all 36 eyes the mean preoperative visual acuity was 20/1233, and the mean final visual acuity was 20/62 (P < 0.0001). Eyes that had a macula-off retinal detachment develop had worse final visual outcomes (20/264; P = 0.01), as did eyes that had proliferative vitreoretinopathy develop (20/129; P = 0.04). CONCLUSIONS Acute, spontaneous, nontraumatic posterior vitreous separation with dense fundus-obscuring vitreous hemorrhage is associated with a high incidence of retinal tears and detachment. Close follow-up with clinical examination and ultrasonography is necessary, because many of these eyes may eventually require surgical intervention. Aggressive management with early vitrectomy should be considered when there is a history of retinal detachment in the contralateral eye.

Evolution of Retinal Detachment in Posterior Retinopathy of Prematurity: Impact on Treatment Approach

PURPOSE To provide insight into the course of retinal detachment in eyes with aggressive posterior retinopathy of prematurity (APROP). DESIGN Prospective, multicenter, masked clinical trial. METHODS Multicenter trial based on serial digital photographic imaging detailing five infants (in the Photographic Screening for Retinopathy of Prematurity [PHOTO-ROP] Study) in whom bilateral retinal detachment developed during the course of the study. RESULTS Retinal detachment developed in both eyes (n=10) of all five infants despite peripheral retinal laser ablation. The mean birth weight was 651.4+/-45.30 g (range, 601 to 718 g), and the mean gestation was 26.75+/-0.96 weeks (range, 24 to 26 weeks). APROP (flat neovascularization) was present in all eyes at the time of treatment. Laser treatment was performed at a mean postconceptual age of 37.25+/-1.8 weeks (range, 35 to 39.57 weeks). Plus disease resolved initially and then recurred (mean, 9.5 days) with progression to retinal detachment; the mean postconceptual age at the time of retinal detachment was 41.42+/-3.6 weeks (range, 36 to 47.29 weeks). Untreated avascular retina became visible with regression of flat preretinal neovascularization. All 10 eyes showed preretinal vitreous organization (most prominent nasally) along the retinal surface without significant transvitreal components. CONCLUSIONS Eyes with APROP may follow an atypical course after laser ablation. Such eyes may still fare poorly, even when plus disease wanes. Additional laser to avascular retina may be necessary after the overlying flat stage 3 neovascularization regresses. The absence of obvious fibrosis at the time of laser should provide no reassurance as to reduced probability of progression to retinal detachment.

The Photographic Screening for Retinopathy of Prematurity Study (Photo-ROP): study design and baseline characteristics of enrolled patients.

Objective: The Photographic Screening for Retinopathy of Prematurity Study (Photo-ROP) sought to evaluate the utility of digital wide-angle photographic fundus screening for retinopathy of prematurity (ROP) as compared to bedside indirect ophthalmoscopy. This article describes the study design and presents baseline characteristics of the subjects. Design: Prospective, multicenter, masked, Internet-based clinical trial. Participants: Premature infants <31 weeks postmenstrual age at birth and <1000 g birthweight. Interventions: Examinations began at 31 weeks postmenstrual age or 4 weeks postnatal age, whichever was later. Both eyes of all infants were imaged with a panoramic fundus imaging system followed by indirect ophthalmoscopic fundus examination. Images were transmitted via Internet to the Reading Center for interpretation by masked graders. Clinical interpretations based on indirect ophthalmoscopy were recorded for comparison with the Reading Center determinations. Examinations were performed weekly for 10 weeks or until an infant was discharged from the hospital. Main outcome measure: Sensitivity, specificity, and positive and negative predictive values of Reading Center image interpretations were compared to clinical impressions based on bedside indirect ophthalmoscopy. Results: Enrollment began in February 2001 and was completed in February 2002. The target number of infants was 50, and 62 were enrolled. Of those enrolled, 51 infants (102 eyes) were considered eligible, and are the subject of this article. Mean postmenstrual age (± SD) at time of delivery was 26.80 ± 1.73 weeks (median = 26.86 weeks, interquartile range [IQR] = 2.43 weeks). Mean postmenstrual age at first examination (± SD) was 32.19 ± 2.86 weeks (median = 31.71 weeks, IQR = 2.29 weeks). Mean birthweight (± SD) was 830.51 ± 219.57 g (median = 817 g, IQR = 225 g). Female infants comprised 49.02% of the patients. Race distribution was as follows: white 45.10%, African or black 39.22%, Hispanic 3.92%, Asian 9.80%, and other races 1.96%. Mean follow-up (± SD) was 5.73 ± 3.22 weeks (median = 6 weeks, IQR = 5, range = [1, 15]). Conclusions: The Photo-ROP Study Cooperative Group successfully recruited and enrolled at-risk premature infants into a longitudinal, prospective clinical trial comparing two different diagnostic approaches. Technology employed in this study is comparable to that currently available. Design issues for this trial included establishing the information technology infrastructure for an ROP study based on digital imaging, defining the study endpoints, estimating event rates, defining a standardized imaging protocol, and defining standards for interpretation of image quality and clinical findings.

Diversity of retinal vascular anomalies in patients with familial exudative vitreoretinopathy.

PURPOSE To describe the diversity of clinical findings associated with familial exudative vitreoretinopathy (FEVR) using wide-field angiography and to update the current classification system. DESIGN Retrospective case series at a single tertiary referral vitreoretinal practice. PARTICIPANTS A total of 174 eyes of 87 subjects were studied. METHODS A retrospective chart review was conducted of patients with a diagnosis of FEVR between January 2011 and January 2013 at a single tertiary care retina practice. Data were collected from patient charts, including sex, gestational age at birth, age at presentation, referring diagnosis, family history, prior ocular surgery, clinical presentation, and diagnostic imaging in each eye. Inclusion criteria included clinical diagnosis of FEVR in patients referred to our clinic for evaluation of decreased vision. Patients were excluded if a diagnosis of FEVR could not be made. MAIN OUTCOME MEASURES Clinical and angiographic findings. RESULTS A total of 87 subjects met the inclusion criteria for this study. A broad spectrum of previously undescribed clinical and angiographic findings were associated with FEVR on wide-field angiography. These findings can be grossly divided into anatomic and functional changes. Anatomic changes include aberrant circumferential peripheral vessels, venous and arterial tortuosity, late-phase disc leakage, central and peripheral telangiectasias, capillary anomalies, and capillary agenesis. Functional changes include venous-venous shunting, delayed arteriovenous transit, and delayed or absent choroidal perfusion on fluorescein angiography. CONCLUSIONS Familial exudative vitreoretinopathy has a wide range of unrecognized or under-recognized clinical and angiographic findings that are easily identified using wide-field fluorescein angiography. These novel findings have led to an update of the original FEVR classification scheme and more complete characterization of early stages of FEVR.

High Prevalence of Peripheral Retinal Vascular Anomalies in Family Members of Patients with Familial Exudative Vitreoretinopathy

OBJECTIVE To describe the prevalence and severity of familial exudative vitreoretinopathy (FEVR) in asymptomatic relatives of known symptomatic FEVR patients. DESIGN Uncontrolled and retrospective case series at a single tertiary referral vitreoretinal practice. PARTICIPANTS A total of 148 eyes of 74 subjects were studied. METHODS A retrospective chart review was conducted of patients with a diagnosis of FEVR between January 2011 and January 2013 at a single tertiary care retina practice. Data were collected from patient charts, including sex, gestational age at birth, age at presentation, referring diagnosis, family history, prior ocular surgery, clinical presentation, and diagnostic imaging in each eye. Inclusion criteria included confirmed clinical diagnosis of FEVR in patients referred to our clinic for evaluation of decreased vision. Patients were excluded if a definitive diagnosis of FEVR could not be made. MAIN OUTCOME MEASURES Clinical and angiographic findings. RESULTS A total of 74 subjects from 17 separate families met the inclusion criteria for this study. There were an average of 4.4 subjects per family included in this study. The cohort was 55% male and included 17 patients and 57 family members who agreed to undergo genotyping, examination, and diagnostic imaging. Forty-three percent of FEVR patients had detectable mutations in FZD4, NDP, or TSPAN12. Only 8% of the cohort reported a positive family history of FEVR in a first-degree relative. Among the index patients, 76% had clinical stage 3, 4, or 5 FEVR and 24% had stage 1 or 2 FEVR. Among the asymptomatic family members screened, 58% demonstrated clinical or angiographic findings consistent with stage 1 or 2 FEVR and 21% demonstrated clinical or angiographic findings consistent with stage 3, 4, or 5 FEVR. CONCLUSIONS Asymptomatic family members of FEVR patients frequently have early manifestations of FEVR (stage 1 or 2). Early-stage FEVR may progress to more advanced stages, which can result in vision loss. These data support the use of angiographic screening and clinical examination in immediate relatives of patients with symptomatic FEVR.

The Microsurgical Safety Task Force: Evolving Guidelines for Minimizing the Risk of Endophthalmitis Associated With Microincisional Vitrectomy Surgery

The Microsurgical Safety Task Force: Evolving Guidelines for Minimizing the Risk of Endophthalmitis Associated With Microincisional Vitrectomy Surgery V itrectomy surgery is performed 250,000 times per year in the United States and 500,000 times per year world-wide for a variety of vitreoretinal pathologic conditions. Traditionally, vitrectomy surgery has been performed with 20-gauge (20-G) instrumentation, first by creating conjunctival peritomies and then constructing 3 20-G scleral incisions through the pars plana to allow access to the vitreous cavity. The conjunctival peritomies and three sclerotomy sites are closed with sutures at the conclusion of the surgery. In contrast to 20-G surgery, 25-gauge (25-G) or 23-gauge (23-G) vitrectomy is initiated by placing 3 cannulae through the conjunctiva, sclera, and pars plana. At the conclusion of the procedure, the cannulae are removed, and because of the smaller incision size, the wounds may self-seal without sutures. The development of a 20-G microincisional cannulae system also is now being evaluated. Overall, 25-G and 23-G surgery avoids the need for conjunctival peritomies and their subsequent closure with sutures, avoids the need for sclerotomy sutures, and permits the use of smaller wounds. This, in turn, has the potential to shorten operative times, improve early postoperative visual outcomes, decrease postoperative discomfort, and hasten postoperative recovery. As with most evolutionary routes, the transition to minimally invasive vitrectomy surgery has not been an entirely smooth one. With the new techniques, a collection of new instruments and refinements in the surgical technique have arrived. Today, the popularity of 23-G and 25-G vitrectomy surgery is at its highest level yet and is still rising. During the past 5 years, there has been a rapid adaptation of microincisional vitrectomy and its usage continues to rise.1,2 In 2008, 50% of vitreous surgery incorporated the microincisional technique. According to a survey conducted by the American Society of Retina Specialists, 70% of U.S. surgeons used 25-G technology in 2007.1 In contrast, just 3 years earlier, 70% of surgeons had claimed to have never used the technique.2 The trend of increased usage and expanding indications for small-gauge vitrectomy has been associated with reports of an increased rate of postvitrectomy complications, including early postoperative hypotony, choroidal hemorrhage, and endophthalmitis.3–11 Although all postoperative complications are potentially vision threatening, endophthalmitis is the most dreaded and severe complication of any intraocular procedure and may result in severe vision loss or blindness. Because of several reports of an increased incidence of endophthalmitis with microincisional vitrectomy compared with sutured vitrectomy,7–9 a Microsurgery Safety Task Force was convened; consensus was sought among a panel of vitreoretinal surgeons experienced with both 20-G and small-gauge pars plana vitrectomy (PPV). Objective evidence was sought for all guidelines, but consensus was accepted when evidence remains incomplete. In the absence of either evidence or consensus, this study identifies the outstanding issues in need of further investigation.

Familial Exudative Vitreoretinopathy: Spectral-Domain Optical Coherence Tomography of the Vitreoretinal Interface, Retina, and Choroid

PURPOSE The in vivo microstructural features of familial exudative vitreoretinopathy (FEVR) have not been well described. We present new anatomic features of FEVR with functional and genetic correlations. DESIGN Consecutive, retrospective, observational case series. PARTICIPANTS Patients with FEVR treated from 2009 to 2014. METHODS We identified 346 patients with FEVR. Those imaged with spectral-domain optical coherence tomography (SD OCT) with or without enhanced depth imaging (EDI) were included, and images were correlated with best-corrected visual acuity (BCVA), widefield angiography, fundus autofluorescence (AF), and wnt signaling pathway mutations. MAIN OUTCOME MEASURES Exploratory SD OCT findings and BCVA. RESULTS A total of 225 imaging sessions were acquired in 74 eyes from 41 patients. Mean age was 19.0 years. Sixty-seven eyes (91%) had interpretable images, of which 50 (75%) had anomalous microstructural findings; all eyes with FEVR severity of stage 2 or greater had abnormalities. A broad spectrum of features were identified: various forms of posterior hyaloidal organization, vitreomacular traction (VMT), vitreopapillary traction, vitreo-fold traction, vitreo-laser scar adhesion, diminished foveal contour, persistent fetal foveal architecture, cystoid macular edema (CME), intraretinal exudates and subretinal lipid aggregation, dry or edematous radial folds, and disruption of the ellipsoid zone. Mean foveal, central macular, and choroidal thicknesses were 305±145 μm, 337±160 μm, and 216±64 μm, respectively. In stages 1 to 2, greater foveal and central macular thicknesses (Rho=0.493, 0.544, respectively; both P<0.001) correlated with poorer BCVA, but not choroidal thickness (Rho=0.032; P=0.868). Posterior hyaloidal organization (P<0.001), VMT (P<0.001), CME (P<0.001), exudation (P<0.001), and disruption of the ellipsoid zone (P<0.001) were associated with poorer BCVA. Disruption of the ellipsoid zone (β=0.699; P<0.001) and posterior hyaloidal organization (β=0.289; P=0.011) retained significance in multivariate modeling (R2=0.627; P<0.001). Spectral-domain OCT detected all cases of angiographic edema and areas of outer retinal dysfunction that were hypoautofluorescent on AF. Microstructural-genetic associations were not identified. CONCLUSIONS Spectral-domain OCT imaging identified microstructural anomalies in the majority of patients with FEVR.