Pneumatic retinopexy versus scleral buckling for the management of primary rhegmatogenous retinal detachment.

BACKGROUND AND OBJECTIVE: To compare pneumatic retinopexy (PnR) and scleral buckling (SB) for repair of primary rhegmatogenous retinal detachment. MATERIALS AND METHODS: Single-centre retrospective analysis of patients undergoing PnR and SB. Inclusion criteria comprehend phakic patients with a single retinal break or a group of breaks in detached retina in the same quadrant above the 8- and 4-o'clock meridians. A total of 184 patients were included, respectively 106 underwent PnR and 78 SB. Follow-up time was 6 months. RESULTS: Final visual outcome did not differ significantly between the two procedures (P = 0.12). Single-procedure reattachment rate was significantly higher in SB (94%) than in PnR (68%) (P < 0001). Anatomical success rate was not influenced by macular involving. Reattachment rate in repeated PnR was 95% and in these patients visual outcome did not statistically differ compared to those reattached with first attempt (P = 0.196). Total reattachment rate including repeated procedures was 87% in PnR group and 94% in SB group, the difference was not significant (P = 0.06). CONCLUSION: SB has a higher single reattachment rate than PnR. However, final visual outcomes of both procedures are comparable. In selected cases, PnR can be repeated with a high successful rate.

RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study.

Purpose: To investigate the course of inherited retinal degenerations (IRD) due to mutations in the RPE65 gene. Methods: This longitudinal multicentric retrospective chart-review study was designed to collect best corrected visual acuity (BCVA), Goldman visual field, optical coherence tomography (OCT), and electroretinography (ERG) measurements. The data, including imaging, were collected using an electronic clinical research form and were reviewed at a single center to improve consistency. Results: From an overall cohort of 60 Italian patients with RPE65-associated IRD, 43 patients (mean age, 27.8 ± 19.7 years) were included and showed a mean BCVA of 2.0 ± 1.0 logMAR. Time-to-event analysis revealed a median age of 33.8 years and 41.4 years to reach low vision and blindness based on BCVA, respectively. ERG (available for 34 patients) showed undetectable responses in most patients (26; 76.5%). OCT (available for 31 patients) revealed epiretinal membranes in five patients (16.1%). Central foveal thickness significantly decreased with age at a mean annual rate of -0.6%/y (P = 0.044). We identified 43 different variants in the RPE65 gene in the entire cohort. Nine variants were novel. Finally, to assess genotype-phenotype correlations, patients were stratified according to the number of RPE65 loss-of-function (LoF) alleles. Patients without LoF variants showed significantly (P < 0.05) better BCVA compared to patients with one or two LoF alleles. Conclusions: We described the natural course of RPE65-associated IRD in an Italian cohort showing for the first time a specific genotype-phenotype association. Our findings can contribute to a better management of RPE65-associated IRD patients.

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

PURPOSE: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. METHODS: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. RESULTS: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. CONCLUSION: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.

Dexamethasone Implant Produces Better Outcomes than Oral Acetazolamide in Patients with Cystoid Macular Edema Secondary to Retinitis Pigmentosa.

Purpose: To compare the clinical outcome of intravitreal dexamethasone implant versus oral acetazolamide in patients with cystoid macular edema (CME) secondary to retinitis pigmentosa (RP). Design: Multicenter, prospective, propensity-score-matched, comparative study. Methods: Eyes with RP and CME were treated either with intravitreal dexamethasone implant or with oral acetazolamide (500 mg/day). Patients were evaluated monthly and followed up for 12 months. Primary outcome measures were changes in central retinal thickness and best corrected visual acuity (BCVA). Adverse events were recorded. Results: Propensity score matching resulted in 2 groups of 30 eyes each. All patients completed 12 months of follow-up. Mean central retinal thickness decreased from 535 µm at baseline to 208 µm at month 12 in the dexamethasone implant group and from 519 to 339 µm in the oral acetazolamide group (P < 0.001, Student's t-test). Mean BCVA average change from baseline during the study (area-under-the-curve approach) was -0.084 logarithm of the minimum angle of resolution (logMAR) (+4.2 letters) in the dexamethasone implant group and -0.032 (+1.6 letters) in the oral acetazolamide group (P < 0.05, Mann-Whitney U test). Patients in the dexamethasone implant group required on average 1.7 treatments during 1 year of therapy. Conclusions: In this study, intravitreal dexamethasone implant produced better anatomic and functional improvements over oral acetazolamide in patients affected by CME secondary to RP. Larger, randomized clinical trials with longer follow-up are warranted to confirm these data.

One-Year Safety and Performance Assessment of the Argus II Retinal Prosthesis: A Postapproval Study.

IMPORTANCE: The Argus II Retinal Prosthesis System is indicated for patients with vision loss due to severe to profound outer retinal degeneration, a group with few treatment options. OBJECTIVES: To collect postapproval safety and visual function data for the Argus II. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, postapproval clinical trial conducted at 9 sites in Germany and Italy. Data were collected from December 2, 2011, to September 30, 2017, and patients were followed-up for 12 months or longer. Patients were 25 years or older with severe to profound outer retinal degeneration, some residual light perception or the ability of the retina to respond to electrical stimulation, and a history of useful form vision and were already planning to undergo Argus II implantation. MAIN OUTCOMES AND MEASURES: The primary end point of this study was the nature and rate of adverse events. Secondary end points included 3 visual function tests: square localization (SL), direction of motion, and grating visual acuity (GVA). RESULTS: Forty-seven patients were followed for 12 months or longer after implant. Mean (SD) age was 56 (12) years, 37 (79%) had retinitis pigmentosa, and 27 (57%) were male. Through the first 12 months postimplantation, 23 patients (49%) experienced 51 nonserious adverse events and 12 (26%) experienced 13 serious adverse events (SAEs), 9 of which were judged to be related to the Argus II, and 4 of which were judged to be related to the procedure. The most common SAE was conjunctival erosion, reported in 4 patients. No significance testing was done for group analysis for the SL or direction-of-motion tests. When averaged across the group, patients' accuracy on the SL test, but not on the direction-of-motion test, appeared better when the Argus II was on than when it was switched off. For GVA, more patients at each point in time achieved the 2.9 GVA cutoff in the implanted eye when the Argus II was on compared with it switched off. CONCLUSIONS AND RELEVANCE: Safety and visual function outcomes in this clinical practice setting cohort of patients with Argus II implants were consistent with previously reported results. Longer follow-up of these patients and data from additional patients are required to better outline the risks and benefits of this approach to addressing blindness secondary to severe-to-profound outer retinal degeneration. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01490827.

Optical coherence tomography imaging in the management of the Argus II retinal prosthesis system.

PURPOSE: To report a real-life experience with the Argus II retinal prosthesis system in blind patients with end-stage retinitis pigmentosa (RP) or choroideremia (CHM), focusing on the pivotal role of optical coherence tomography (OCT) in both preoperative and postoperative management. METHODS: This hospital-based case series included 3 blind patients who were uneventfully implanted with Argus II epiretinal device. These patients (2 with RP and 1 with CHM) were selected during the Argus™ II Retinal Prosthesis System PostMarket Surveillance Study Protocol. Complete screening procedures had involved 66 eyes of 33 patients afferent to the Center for Retinitis Pigmentosa of the Veneto Region. RESULTS: Preoperative OCT examination resulted in the exclusion of 8 eyes in 4 patients with bilateral posterior staphyloma diagnosing unexpected staphylomatous macular patterns in 2 patients with RP and no sign of pathologic myopia. Postoperative OCT study of Argus II proximity to retinal surface indicated a plausible correlation between electrode-retina distance and perceptual threshold in 2 of our 3 patients. In particular, during the first 6 months of follow-up, the patient with the closest contact between device and macula showed a continuous vision-related improvement in the performance of several real-life tasks. CONCLUSIONS: The present findings illustrate the modalities by which each different OCT examination is an essential tool to optimize safety and efficacy profiles during Argus II protocol. Optical coherence tomography will be crucial for future investigative approaches on patient selection criteria and next-generation implant design.

Identification of novel X-linked gain-of-function RPGR-ORF15 mutation in Italian family with retinitis pigmentosa and pathologic myopia.

The aim of this study was to describe a new pathogenic variant in the mutational hot spot exon ORF15 of retinitis pigmentosa GTPase regulator (RPGR) gene within an Italian family with X-linked retinitis pigmentosa (RP), detailing its distinctive genotype-phenotype correlation with pathologic myopia (PM). All members of this RP-PM family underwent a complete ophthalmic examination. The entire open reading frames of RPGR and retinitis pigmentosa 2 genes were analyzed by Sanger sequencing. A novel frame-shift mutation in exon ORF15 of RPGR gene (c.2091_2092insA; p.A697fs) was identified as hemizygous variant in the male proband with RP, and as heterozygous variant in the females of this pedigree who invariably exhibited symmetrical PM in both eyes. The c.2091_2092insA mutation coherently co-segregated with the observed phenotypes. These findings expand the spectrum of X-linked RP variants. Interestingly, focusing on Caucasian ethnicity, just three RPGR mutations are hitherto reported in RP-PM families: one of these is located in exon ORF15, but none appears to be characterized by a high penetrance of PM trait as observed in the present, relatively small, pedigree. The geno-phenotypic attributes of this heterozygosity suggest that gain-of-function mechanism could give rise to PM via a degenerative cell-cell remodeling of the retinal structures.

Good epidemiologic practice in retinitis pigmentosa: from phenotyping to biobanking.

Inherited retinal dystrophies, such as retinitis pigmentosa (RP), include a group of relatively rare hereditary diseases caused by mutations in genes that code for proteins involved in the maintenance and function of the photoreceptor cells (cones and rods). The different forms of RP consist of progressive neurodegenerative disorders which are generally related to various and severe limitations of visual performances. In the course of typical RP (rod-cone dystrophy), the affected individuals first experience night-blindness and/or visual field constriction (secondary to rod dysfunctions), followed by variable alterations of the central vision (due to cone damages). On the other hand, during the atypical form of RP (cone-rod dystrophy), the cone's functionalities are prevalently disrupted in comparison with the rod's ones. The basic diagnosis of RP relies upon the documentation of unremitting loss in photoreceptor activity by electroretinogram and/or visual field testing. The prevalence of all RP typologies is variably reported in about one case for each 3000-5000 individuals, with a total of about two millions of affected persons worldwide. The inherited retinal dystrophies are sometimes the epiphenomenon of a complex framework (syndromic RP), but more often they represent an isolated disorder (about 85-90 % of cases). Although 200 causative RP mutations have been hitherto detected in more than 100 different genes, the molecular defect is identifiable in just about the 50% of the analyzed patients with RP. Not only the RP genotypes are very heterogeneous, but also the patients with the same mutation can be affected by different phenotypic manifestations. RP can be inherited as autosomal dominant, autosomal recessive or X-linked trait, and many sporadic forms are diagnosed in patients with no affected relatives. Dissecting the clinico-genetic complexity of RP has become an attainable objective by means of large-scale research projects, in which the collaboration between ophthalmologists, geneticists, and epidemiologists becomes a crucial aspect. In the present review, the main issues regarding clinical phenotyping and epidemiologic criticisms of RP are focused, especially highlighting the importance of both standardization of the diagnostic protocols and appropriateness of the disease's registration systems.

Effect of incision size and site on corneal endothelial changes in cataract surgery.

PURPOSE: To compare endothelial damage induced by different cataract incision sites and sizes using specular microscopy. SETTING: Department of Ophthalmology, Hospital of San Donà di Piave, Venice, Italy. METHODS: Eighty-one eyes having phacoemulsification were randomly assigned to 1 of 3 groups of 27 eyes each: 3.5 mm clear corneal incision (CCI) with silicone foldable intraocular lens (IOL) implantation; 5.5 mm sutured CCI with poly(methyl methacrylate) (PMMA) IOL implantation; 5.5 mm scleral tunnel with PMMA IOL implantation. All incisions were centered at the 120-degree semimeridian; that is, they were superotemporal in right eyes and superonasal in left eyes. Noncontact specular microscopy was performed in the center and at the 12 o'clock position preoperatively as well as 1 week and 1, 3, and 12 months postoperatively. The endothelial cell density, mean cell area, cell size variation coefficient, percentage of hexagonality, and corneal thickness were considered. RESULTS: Progressive endothelial cell loss and an increase in mean cell area occurred in all groups during the follow-up. The cell loss percentages relative to the endothelial center appeared similar among the groups and slightly although not significantly lower in the scleral tunnel group. The scleral tunnel group had a statistically significant lower cell loss percentage at the 12 o'clock position than the 2 CCI groups at all follow-ups. CONCLUSIONS: The scleral tunnel group had less postoperative endothelial damage than the 2 CCI groups, with a statistically significant difference at the 12 o'clock position. This is probably because the scleral tunnel incision is placed more posteriorly and therefore induces less direct and indirect endothelial trauma.