THE PROGRESSION OF MACULAR STRUCTURAL AND FUNCTIONAL CHANGES IN LATE-ONSET RETINAL DEGENERATION.

BACKGROUND/PURPOSE: To characterize the progression of structural and functional changes in the retinas of a small cohort of unrelated patients with early late-onset retinal degeneration and evaluate these changes as potential biomarkers for future treatment trials. METHODS: Best-corrected visual acuity, contrast sensitivity, Goldman visual fields, retinal sensitivity measurement by mesopic microperimetry, extent of ellipsoid zone disruption using spectral domain optical coherence tomography, and fundus autofluorescence imaging were performed at each biennial visit. PATIENTS: Three unrelated patients with molecularly confirmed late-onset retinal degeneration (S163R mutation in C1QTNF5 ) were prospectively followed for 4 years. RESULTS: The patient's ages were 44, 54, and 62 at baseline. Over the 4-year follow-up period, one patient demonstrated a significant reduction in best-corrected visual acuity (6 Early Treatment of Diabetic Retinopathy Study letters), whereas two patients suffered a significant reduction in contrast sensitivity. Early in the disease, there was a close relationship between ellipsoid zone disruption and a loss in retinal sensitivity. Later in the course of the disease, there were areas outside the zones of ellipsoid zone disruption that also suffered progressive loss of retinal sensitivity, suggesting that ellipsoid zone loss was not the only factor responsible for the loss of retinal sensitivity. Changes in fundus autofluorescence and Goldman visual field loss were not closely related to changes in ellipsoid zone disruption or retinal sensitivity loss. CONCLUSION: This study has found that the monitoring of the progression of ellipsoid zone disruption and changes in mesopic microperimetry may be useful biomarkers in future clinical trials in patients with late-onset retinal degeneration.

An Uncommon Aflibercept Side Effect: Full Thickness Macular Hole Formation After Intravitreal Injections in Patients With Pre-existing Vitreomacular Traction.

Aflibercept is an intravitreally injected anti-vascular endothelial growth factor, commonly used in patients with several retinal pathologies, including neovascular age-related macular degeneration. We report a case series of three patients under treatment with an aflibercept regime for neovascular age-related macular degeneration, who were referred to vitreoretinal service between 2015-2016. In all cases, pre-existing vitreomacular traction was detected with an optical coherence tomography scan. All of them developed full-thickness macular hole after aflibercept intravitreal injections. The combined cataract and macular hole surgery was successful, with improvement in visual acuity. We suggest that dynamic alterations of the size of the pigment epithelium detachment resulting from intravitreal injections might intensify the pre-existing pathological adhesion of the vitreous-retinal interface and subsequently cause the formation of a full-thickness macular hole. Therefore, all practitioners treating patients with aflibercept intravitreal injections and pre-existing vitreomacular traction should be aware of the possible macular hole formation.

CHARACTERIZING THE NATURAL HISTORY OF FOVEAL-SPARING ATROPHIC LATE-ONSET RETINAL DEGENERATION.

PURPOSE: To identify quantifiable markers of disease progression in patients with foveal-sparing atrophic late-onset retinal degeneration using fundus autofluorescence and spectral-domain optical coherence tomography imaging. METHODS: Natural history study evaluating patients within a 3-year interval. Disease progression was assessed based on the area of retinal atrophy, macular topographic distribution of lesions, retinal and choroidal thickness and volume, and choroidal vascularity index. RESULTS: Twenty-four eyes (12 individuals) were included for fundus autofluorescence, and 31 eyes (16 individuals) for spectral-domain optical coherence tomography studies. Measurements were symmetrical between eyes of the same patient. The area of atrophy significantly enlarged (P = 0.002), with a growth rate of 2.67 mm2/year (SD: 2.13; square rooted: 0.57 mm/year, SD = 0.34). Baseline area of atrophy and progression both correlated with age. Most atrophic lesions were found in the temporal macula and progressed nasally at follow-up. Central choroidal and retinal thicknesses and volume in late-onset retinal degeneration cases were significantly reduced compared with controls, but only central retinal thickness decreased significantly at follow-up. CONCLUSION: This study identifies the area of atrophy and central retinal thickness, but not chorioretinal volume or choroidal thickness, as markers of short-term progression in late-onset retinal degeneration. These findings may be useful for disease monitoring and late-onset retinal degeneration interventional studies.

Cataract surgery in patients with late-onset retinal degeneration.

PURPOSE: To review the outcomes in a series of patients with long anterior lens zonular fibers associated with late-onset retinal degeneration who had phacoemulsification cataract surgery. SETTING: Newcastle Eye Centre, Newcastle upon Tyne, United Kingdom. DESIGN: Retrospective case series. METHODS: Inclusion criteria were patients with genetically confirmed late-onset retinal degeneration requiring cataract surgery. Perioperative data relating to surgery were collected. In addition, the corrected distance visual acuity (CDVA) and retinal imaging data were recorded. Selected lens capsules were examined using immunohistochemistry or scanning electron microscopy (SEM). RESULTS: Eleven eyes of 7 patients were included. The long anterior lens zonular fibers made capsulorhexis challenging; however, it was completed safely in all cases. There were no intraoperative or postoperative issues with lens stability. The CDVA improved postoperatively in those cases with intact foveal photoreceptors and retinal pigment epithelium. Over the longer term, the CDVA slowly declined because of progressive atrophy of the macula. Most patients noticed a subjective improvement in vision, even those with advanced disease at baseline. Immunohistochemistry showed that the C1QTNF5 protein was expressed within the lens capsule epithelial cells, although SEM of the long anterior lens zonular fibers showed them to be smaller in diameter than normal anterior lens zonular fibers and to be composed of a helix of fibers. CONCLUSIONS: In this small series of patients with late-onset retinal degeneration, cataract surgery was successfully performed without long-term complications involving intraocular lens stability. The objective improvement in CDVA seemed to be limited to patients with good foveal photoreceptor architecture.

Gas Tamponade for Retinectomy in PVR-Related Retinal Detachments: A Retrospective Study.

INTRODUCTION: The purpose of the study was to evaluate the anatomical and functional results in patients with proliferative vitreoretinopathy (PVR) treated with retinectomy and perfluoro-octane gas (C3F8) as a tamponade agent. METHODS: 12 patients with inferior and anterior complicated PVR-related retinal detachment, who were treated with retinectomy, where C3F8 was used as the tamponade agent were examined. Primary outcome was the anatomical success, while visual acuity, existence of an epiretinal membrane (ERM) and intraocular pressure (IOP) postoperatively were secondary outcomes. RESULTS: The primary success rate was 75% (mean follow-up of 9.8 months). Reoperation was needed on 25% of patients after the retinectomy procedure. Preoperative best corrected visual acuity (BCVA) was poor due to macular involvement in all cases. BCVA was improved in three patients (25%), remained stable in 25% and deteriorated in 16.7%. Two patients were lost during the follow-up period. Postoperative ERM formation was noted in 33.3% of patients. One patient developed hypotony, while no other complications were observed. CONCLUSION: Retinectomy with C3F8 as the tamponade agent provides anatomical and functional restoration at a 75% primary success rate in PVR-related retinal detachment.

OBSERVATION: FLUOCINOLONE ACETONIDE (ILUVIEN) IMPLANT MIGRATION INTO THE ANTERIOR CHAMBER.

PURPOSE: To describe the anterior chamber migration of a fluocinolone acetonide (Iluvien) implant in the context of previous vitrectomy and complicated cataract surgery. METHODS: Retrospective observational case series. Two patients with a history of vitrectomy and complicated phacoemulsification surgery, one of whom had pseudoexfoliation. RESULTS: The implant migrated to the anterior chamber shortly after implantation. One patient had the implant removed after one recurrence; the other used pilocarpine 2% eye drops to reduce the risk of further migration. CONCLUSION: Complicated cataract surgery and vitrectomy can be associated with migration of fluocinolone acetonide implants into the anterior chamber.

Ultra-low dose of intravitreal bevacizumab in the treatment of retinopathy of prematurity.

Intravitreal bevacizumab is an increasingly common treatment choice for posterior retinopathy of prematurity. Despite concern about its systemic effects, there have been few studies on the lowest effective dose. The authors describe a case that was successfully treated with 0.16 mg of bevacizumab, the first time this dose has been reported.

Improvement of retinal function in L-ORD after prolonged dark adaptation.

OBJECTIVE: To describe the changes in dark-adapted (DA) retinal electrophysiological function after prolonged dark adaptation in a cohort of patients with late-onset retinal degeneration (L-ORD). DESIGN: Prospective case series. PARTICIPANTS: Nine patients with either stage 2 or 3 L-ORD. METHODS: International Society for Clinical Electrophysiology of Vision standard DA electroretinograms (ERGs) were performed before and after a period of extended dark adaptation (16 hours) in a cohort of patients heterozygous for the Ser163Arg mutation in C1QTNF5. RESULTS: Rod function was abnormal in 8 of 9 patients after standard (20 min) of dark adaptation. After extended dark adaptation, rod function normalized in 4 patients and there was a mean improvement in the DA 0.01 rod-specific ERG b-wave amplitude of 310% (p = 0.004). A significant improvement in DA 3.0 a-wave ERG amplitude localized the improvement in rod function at the level of the photoreceptor. CONCLUSIONS: This study demonstrates that a significant proportion of rod dysfunction in L-ORD can be reversed by extended dark adaptation and suggests that an abnormality of the visual cycle contributes to the pathogenesis of the disease. These findings would suggest that some retinal function could be restored, even in advanced cases of the disease if a suitable treatment is found.