Macular Retinoschisis from Optic Disc without a Visible Optic Pit or Advanced Glaucomatous Cupping (No Optic Pit Retinoschisis [NOPIR]).

PURPOSE: To review eyes with peripapillary and macular retinoschisis without a visible optic pit or advanced glaucomatous optic atrophy, or No Optic Pit Retinoschisis (NOPIR). DESIGN: Retrospective multicenter case series. SUBJECTS: The study included 11 eyes of 11 patients. METHODS: Retrospective study of eyes with macular retinoschisis without a visible optic pit, advanced optic nerve head cupping, or macular leakage on fluorescein angiography. MAIN OUTCOME MEASURES: Visual acuity (VA), retinoschisis resolution, months to resolution, and recurrence of retinoschisis RESULTS: The mean age was 68.1 ± 17.6 years, mean intraocular pressure was 17.4 ± 3.8 mmHg, and the mean spherical equivalent refractive error was -3.1 ± 2.9 diopters. No subject had pathologic myopia. Seven subjects were treated for glaucoma, and 9 subjects had nerve fiber layer defects on OCT. All eyes had retinoschisis in the outer nuclear layer (ONL) in the nasal macula and extending to the edge of the optic disc, and 8 subjects had fovea-involving retinoschisis. Three nonfoveal and 4 fovea-involved eyes were observed, and 4 fovea-involved eyes with vision loss underwent surgery. Surgery involved preoperative juxtapapillary laser followed by vitrectomy and membrane and internal limiting membrane peeling with intraocular gas and face-down position. The mean baseline VA was significantly worse in the surgery group than that in the observation group (P = 0.020). Retinoschisis resolved and vision improved in all surgical cases. The mean resolution time for the surgery group was 2.75 ± 0.96 months, which was shorter than that for the observation group (28.0 ± 21.2 months; P = 0.014). No eye developed recurrence of the retinoschisis after surgery. CONCLUSIONS: Peripapillary and macular retinoschisis can develop in eyes without a visible optic pit or advanced glaucomatous cupping. Eyes without foveal involvement and those with foveal involvement but only mild decrease in vision can be observed for spontaneous resolution. If there is persistent foveal involvement with vision loss, surgery can improve vision by resolving the macular retinoschisis. Surgery for fovea-involved macular retinoschisis without a visible optic pit resulted in faster anatomic resolution and better vision recovery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

What do Cochrane systematic reviews say about interventions for age-related macular degeneration?

BACKGROUND: Age-related macular degeneration (AMD) is the third largest cause of blindness worldwide, accounting for 8.7% of all cases. A considerable number of preventive or therapeutic interventions have been used for AMD. OBJECTIVE: This study presents a critical view of the interventions that have been assessed through Cochrane systematic reviews. DESIGN AND SETTING: Review of systematic reviews, conducted in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP). METHODS: Review of Cochrane systematic reviews about interventions for AMD. RESULTS: The 18 systematic reviews included assessed the effects of surgical techniques, laser/photo/radiotherapy, intravitreal injections, systemic drugs and phytotherapy/vitamins/supplements. CONCLUSION: The Cochrane systematic reviews found evidence that use of bevacizumab, ranibizumab, pegaptanib, laser photocoagulation, photodynamic therapy and multivitamin compounds may present some benefits for treating AMD. There was insufficient evidence for supporting the use of macular translocation, submacular surgery, steroid implantation, radiotherapy, intravitreal aflibercept, interferon alfa, statins or omega-3 fatty acids for treating AMD; or the use of multivitamin antioxidant vitamins or mineral supplementation for preventing AMD. Future randomized controlled trials are imperative to reduce the uncertainty in several clinical questions regarding AMD.

Stereological Method in Optical Coherence Tomography for In Vivo Evaluation of Laser-Induced Choroidal Neovascularization.

BACKGROUND AND OBJECTIVE: To evaluate a stereological method in optical coherence tomography (OCT) as an in vivo volume measurement of laser-induced choroidal neovascularization (L-CNV) lesion size. PATIENTS AND METHODS: Laser photocoagulation was applied in rats to rupture Bruch's membrane and induce L-CNV. In vivo OCT images of neovascular lesions were acquired with a spectral-domain OCT system at days 0, 3, 7, 10, and 14 after laser surgery. A stereological image-processing method was used to calculate lesion volumes from the OCT images. Rats were euthanized at day 14, and confocal microscopy was used to obtain accurate volume measurements of the lesions ex vivo. Lesion sizes calculated from OCT and confocal were compared. RESULTS: In vivo assessment by OCT allowed three distinct stages of L-CNV to be visualized: the initial early reaction, neovascular proliferation, and regression. At day 14, correlations between OCT and confocal lesion volumes showed a positive association (Pearson's r = 0.50, P < .01). Except for the largest lesions, volumes measured by OCT were statistically similar to those measured by the confocal gold standard (P = .90). CONCLUSION: The stereological approach used to measure neovascular lesion volume from OCT images offers an accurate means to track L-CNV lesion size in vivo. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e65-e74.].

Macular pigment density variation after supplementation of lutein and zeaxanthin using the Visucam® 200 pigment module: Impact of age-related macular degeneration and lens status.

PURPOSE: To assess the evolution of macular pigment optical density (MPOD) following supplementation with various macular formulations obtained with the Visucam® 200, and to study the factors affecting MPOD measurements. MATERIALS AND METHODS: In this prospective, randomized, double-masked multicenter study, patients were divided into 2 groups: group A (patients without retinal pathology who underwent cataract surgery 1 month previously) and group B (patients with neovascular age-related macular degeneration [AMD] in one eye). In each group, half of the patients were randomly assigned to receive a food supplementation either with or without carotenoids (5mg of Lutein and 1mg of Zeaxanthin). Outcome measures included MPOD responses obtained with the Visucam® 200 for one year. RESULTS: In total, 126 subjects (52 men, 74 women) with a mean age of 75.3±7.61 years were enrolled. Mean MPOD values at the time of inclusion were statistically lower in group A (0.088 density unit [DU]) compared to group B (0.163 DU, P<0.05). No statistically significant increase in MPOD was noted in either group, even after discontinuation of the supplementation. By multiple regression analysis, age, female gender, lens status and the presence of AMD seemed to significantly affect MPOD measurements. CONCLUSION: No significant improvement in MPOD seems to be detected with the Visucam® 200 after carotenoid supplementation. The MPOD measurement seems to be highly affected by cataract extraction and the presence of AMD.

Electronic restoration of vision in those with photoreceptor degenerations.

Complete loss of vision is one of the most feared sequelae of retinal disease. Currently, there are few if any treatment options available to patients that may slow or prevent blindness in diseases caused by photoreceptor loss, such as retinitis pigmentosa and age-related macular degeneration. Electronic restoration of vision has emerged over recent years as a safe and viable option for those who have lost substantial numbers of photoreceptors and who are severely vision impaired. Indeed, there has been a dramatic increase in our understanding of what is required to restore vision using an electronic retinal prosthesis. Recent reports show that for some patients, restoration of vision to the point of reading large letters is possible. In this review, we examine the types of implants currently under investigation and the results these devices have achieved clinically. We then consider a range of engineering and biological factors that may need to be considered to improve the visual performance of newer-generation devices. With added research, it is hoped that the level of vision achieved with newer generation devices will steadily improve, resulting in enhanced quality of life for those with severe vision impairment.

Expanded polytetrafluoroethylene as a substrate for retinal pigment epithelial cell growth and transplantation in age-related macular degeneration.

BACKGROUND: Retinal pigment epithelial (RPE) transplantation presents a potential treatment for age-related macular degeneration (AMD). A suitable transplant membrane that can support an intact functioning RPE monolayer is required. Expanded polytetrafluoroethylene (ePTFE) possesses the physical properties required for a transplanting device; however, cells do not attach and spread on ePTFE. This study investigated the ability of surface-modified ePTFE to optimise the growth and function of healthy RPE monolayers. METHODS: ePTFE discs were modified by ammonia gas plasma treatment. ARPE-19 cells were seeded on the membranes and maintained in media supplemented with retinoic acid and reduced serum. Cell number, morphology and proliferation were analysed. RPE monolayer function was investigated through formation of cell-cell junctions and phagocytosis of photoreceptor outer segments (POS). RESULTS: Ammonia gas plasma treatment resulted in enhanced cell growth and good monolayer formation with evidence of cell-cell junctional proteins. Furthermore, RPE monolayers were able to phagocytose POS in a time-dependent manner. CONCLUSIONS: ePTFE can be surface-modified to support an intact functional monolayer of healthy RPE cells with normal morphology and the ability to perform RPE-specific functions. Following further investigation ePTFE may be considered for use in transplantation.

Combined therapy in exudative age-related macular degeneration.

PURPOSE: Therapeutic options in active exudative age-related macular degeneration (AMD) are following means used to destroy the choroidal neovascularization (CNV) lesion: laser photocoagulation, radiotherapy, transpupillary thermotherapy, photodynamic therapy (POT) or removal of neovascular membrane through vitreoretinal surgery. Another possibility is to suppress the development of neovasculanization through intravitreal administration of anti-VEGF agents: ranibizumab, bevacizumab (off-label), sodium pegaptanib or steroids (off-label). The aim of this paper is to present the early phase of treating exudative AMO with combined therapy: photodynamic therapy with intravitreal ranibizumab injection. MATERIAL AND METHODS: Our observation is based on three clinical cases. Observations are being carried out on larger patient groups according to the treatment scheme presented in this paper. RESULTS: In the three cases described one POT procedure and the saturation phase of three ranibizumab injections allowed a significant improvement in visual acuity and closure of CNV leakage confirmed by fluorescein angiography (FA) and optical coherence tomography (OCT). Treatment is being continued according to AMO activity: next POT in case of leakage in FA, another ranibizumab injection according to PRONTO study reinjection criteria. CONCLUSIONS: The pathomechanism of exudative AMB confirms reasonability of combined treatment. Considering the stages of neovascularization in exudative AMO. VEGF inhibition combined with POT has a synergistic action and increases the effectiveness of both therapies alone. L.arge clinical studies (FOCUS) show that combined therapy reduces the number or required POT procedures. In combined therapy modification of POT parameters should be considered: reduction of energy and laser exposure time.

Age-related macular degeneration: current and novel therapies.

Age-related macular degeneration (AMD) is a leading cause of vision loss in people over the age of 60 with a prevalence that continues to rise, particularly in industrialized nations. Although treatments for AMD were once limited, with disappointing clinical results, new treatments have emerged for both the nonexudative and exudative forms of the disease, which have improved prognostic outcomes. These treatments include nutritional supplementation, antioxidant prophylaxis, and intravitreal injection of medications that inhibit aberrant vascular proliferation. This review serves as a summary of the current and experimental therapies for both exudative and nonexudative AMD. Although a number of challenges and clinical questions remain, the future of treating AMD appears promising particularly as we gain further insights into the genetic and biochemical pathways of the disease.

[A discussion about key issues in retinal prosthesis].

Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are two predominant causes of visual deterioration. Retinal prosthesis embeds a micro-electric chip or a micro-photoelectric diode array in the sub-retina or epi-retina, which is used to stimulate the remainder of inner retina, so as to restore some degree of sight. Retinal prosthesis has attracted most attention in the field of artificial visual function recovery, and along with deep-going research, many issues need to be resolved. In this paper, the theory of retinal prosthesis and the status quo of research in many countries are introduced, the key issues which influence the application of the retinal prosthesis are discussed in detail, and some notions and advices are presented.

A prospective randomised study on low-dose transpupillary thermotherapy versus photodynamic therapy for neovascular age-related macular degeneration.

AIM: To compare the efficacy of low-dose transpupillary thermotherapy (TTT) and verteporfin photodynamic therapy (PDT) in patients with occult neovascular age-related macular degeneration (AMD). METHODS: Patients were randomised to receive either low-dose TTT (136 mW/mm) (and sham PDT) (n = 52) or PDT (and sham TTT) (n = 46) with retreatment if leakage was documented by fluorescein angiography. At baseline and at every follow-up, best corrected visual acuity (BCVA) was measured with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, lesion size on fluorescein angiography and foveal thickness with optical coherence tomography. The primary outcome measure was the proportion of patients who lost <15 letters at 12 months' follow-up. Secondary outcome measures included the proportion of patients who gained >/=0 letters, the change in mean lesion size and the change in foveal thickness at 12 months' follow-up. RESULTS: The percent of patients losing fewer than 15 letters at 12 months was 75.0% in the TTT group and 73.9% in the PDT group (p>0.05). The percent of patients with preserved or improved BCVA was 36.5% in the TTT group versus 23.9% in the PDT group (p>0.05). The mean decrease in foveal thickness was 15% for TTT and 24% (p>0.05) for PDT-treated patients, and the mean increase in total lesion area was -0.7% and -1.1% (p>0.05), respectively. CONCLUSION: In this prospective, randomised trial low-dose TTT and PDT appeared to be equally efficient at stabilising visual acuity in patients with occult neovascular AMD. Low-dose TTT may be considered as an alternative to PDT in this set of patients and also as an adjuvant to pharmacotherapy.

[Age-related macular degeneration]. / La dégénérescence maculaire liée à l'âge.

PURPOSE: Age-related macular degeneration is the commonest overall cause of irreversible blindness in patients aged 50 or over in the Western world. CURRENT KNOWLEDGE AND KEY POINTS: Because of the interaction of genetic and environmental origin, the pathogenesis of this affection remains imperfectly elucidated. The disease has been traditionally classified into early and late stages with its dry and wet forms. In association with fluorescein angiography, essential for diagnosis, green indocyanin angiography and optical coherence tomography made it possible to better know the clinical forms of the disease. Patients with age-related maculopathy should consider taking a dietary supplement such as that used in the age-related eye disease study. Exudative age-related macular degeneration is approached depending on the type and localisation of the choroidal new vessels. Laser photocoagulation has only been shown to be beneficial for extra and juxtafoveal classic lesions. Photodynamic therapy with verteporfin is effective in the management of eyes with subfoveal predominantly classic lesions. The encouraging results of new therapeutic with antiangiogenic aiming against vascular endothelial growth factor are a hope to preserve the sight of our patients. FUTURE PROSPECTS AND PROJECTS: In the future, many therapeutics inhibiting neo-vessels will widen our therapeutic options in the treatment of exsudative age-related macular degeneration.

The burden of age-related macular degeneration.

As age-related macular degeneration (AMD) becomes more prevalent as a result of longer life expectancy and the number of elderly people worldwide, it will become increasingly important to understand its potential health and economic impact for appropriate healthcare planning. This review identified published literature on costs and resource use associated with AMD. Despite the increasing prevalence of AMD, the worldwide burden of illness is unknown. Several studies of direct medical costs, both those associated with ophthalmic care and those associated with other care, have been conducted and have identified increased medical care associated with AMD. Direct non-medical costs include the cost for vision aids; while these costs may be substantial, they are difficult to quantify as no comprehensive sources track the distribution or use of vision aids. Because AMD is uncommon among people of working age, there is less concern regarding the impact of indirect (workplace) costs among AMD patients. However, indirect costs are incurred by caregivers who leave the workforce early or change their work patterns in order to provide assistance to AMD patients; the magnitude of caregiver-related costs is unknown. The cost effectiveness of some interventions for AMD has been explored. Supplementation with zinc and antioxidants for non-exudative (dry) AMD has been shown to result in an acceptable cost per QALY and is considered cost effective. Studies suggest that laser photocoagulation is cost effective but that photodynamic therapy with verteporfin appears to be cost effective only among patients with good visual acuity at baseline or when models extend longer than 5 years. Further research is needed to integrate the information on various components of AMD-related costs into a comprehensive burden of illness estimate and to evaluate basic utility assumptions in existing models.

[Transpupillary thermotherapy for occult choroidal neovascularizations]. / Transpupillare Thermotherapie bei okkulten subretinalen Neovaskularisationen.

PURPOSE: This contribution describes the results of transpupillary thermotherapy (TTT) for age-related exudative macular degeneration (AMD) with regression. PATIENTS AND METHODS: In exudative AMD with occult choroidal neovascularization (CNV), transpupillary thermotherapy (TTT) was performed using a diode laser (Iridex) in unselected patients. Before therapy and 1, 3, and 6 months after the initial treatment the patients were examined clinically. Additionally threshold testing in the 10 degrees field (Humphrey) and fluorescein angiographies were documented at all check-ups. RESULTS: With respect to vision, differences in the slope of the regression lines between small, medium, and large CNV were significant (p<0.001). The slope of the regressions lines was significant except for small CNV. Regarding the 10 degrees field (Humphrey), there were no statistical differences in the slope of the regression lines (p=0.867). CONCLUSIONS: Transpupillary thermotherapy with small CNV did not show a statistically significant decrease of VA. Thus, in clinical terms early treatment of occult CNV with TTT seems to be able to prevent a further loss of visual acuity.

Evaluation of trans-scleral diode laser using diopexy probe for subfoveal choroidal neovascular membrane in age-related macular degeneration.

OBJECTIVE: To evaluate safety and short-term visual and fluorescein angiographic effects of trans-scleral diode laser photocoagulation in patients with subfoveal choroidal neovascularization from age-related macular degeneration (ARMD). BACKGROUND DATA: The visual outcome following treatment of subfoveal choroidal neovascularization in ARMD is still unsatisfactory. Various forms of therapy such as laser treatment, photodynamic therapy, radiation therapy, transpupillary thermotherapy, and surgical excision have been tried with variable results. MATERIALS AND METHODS: Patients with subfoveal choroidal neo-vascularization were treated with trans-scleral diode laser using the diopexy probe under indirect ophthalmoscopic visualization and followed up at 2, 6, and 12 weeks. Standardized protocol refraction, visual acuity testing, reading speed, contrast requirement measurement, ophthalmic examinations, color fundus photographs, and fluorescein angiogram were used to evaluate the results of treatment. RESULTS: Eighteen eyes of 18 patients were included in the study between April 2000 and May 2002. At 12 weeks, 81.5% patients showed stabilization (+/-5 letters) in letter visual acuity score, and one patient showed improvement (gain of more than five letters) in letter visual acuity score. Reading speed levels and contrast requirement were found to be similar to pre-laser level at 3 months followup. At 12 weeks, moderate fluorescein leakage was seen in one eye, minimal leakage was seen in five eyes, absence of leakage was seen in 10 eyes, and progression was seen in two eyes. CONCLUSION: Transcleral diode laser treatment of subfoveal choroidal neovascular membranes in ARMD may be an effective as well as safe alternative in the management of these patients.

Case selection in macular relocation surgery for age related macular degeneration.

BACKGROUND: To date there has been no randomised controlled trial demonstrating the safety and efficacy of macular relocation surgery (MRS) for age related macular degeneration (AMD). Vision can be improved in some patients and made worse in others despite successful surgery or because of complications. PURPOSE: To determine which patients would benefit from MRS. METHODS: Twenty nine patients with exudative AMD took part in a prospective, non-comparative, interventional study. Macular relocation surgery involved phacoemulsification, vitrectomy, 360 degrees retinotomy, excision of choroidal neovascular membrane, and macular relocation using an infusion of 5-fluorouracil and low molecular weight heparin as adjuvant to prevent proliferative vitreoretinopathy. Patients underwent protocol refraction preoperatively and six-monthly postoperatively by designated optometrists. Preoperative fundus fluorescein angiograms were read by masked observers and the lesions were classified according to a set protocol. The main outcome measures were visual improvement, final vision of better than 20/400, reading speed, critical print size. Logistic and multiple stepwise linear regressions were used to identify independent factors which predicted the main outcomes. RESULTS: Preoperative visual acuity (20/120 or worse) and lesion type (predominantly classic or submacular haemorrhage) were significantly associated with visual improvement (coefficient of regression B = 26.8, p<0.001 and B = 14.9 with p = 0.045 respectively). There were no significant independent factors which predicted a final distance logMAR visual acuity of 1.3 (20/400) or any arbitrary definition of blindness. CONCLUSIONS: The study showed that it was possible to select cases that were more likely to experience an improvement in vision following MRS.

[The role of surgery in the treatment of age-related macular degeneration]. / Place de la chirurgie dans le traitement de la DMLA.

The place of surgery in DMLA amounts to the surgical treatment of choroidal neovascular membranes and submacular hemorrhage. After a brief historical review, the different techniques currently used are described, but indications have become rarer since the development of dynamic phototherapy. However, despite a high complication rate, these surgical methods should not disappear from our therapeutic arsenal because they have proved their ability to restore good visual acuity.

New treatments in age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of legal blindness in individuals 50 years and older in the developed world. Choroidal neovascularization (CNV) in exudative AMD is responsible for the majority of severe vision loss. Until recently, laser photocoagulation was the only well-established and widely accepted treatment for CNV. However, it is beneficial only for a small subset of patients, has a high rate of CNV persistence and recurrence and results in iatrogenic, collateral damage to the overlying retina. These issues make it difficult to recommend in the case of subfoveal lesions. Consequently, numerous experimental therapeutic interventions are under investigation with the common objective of destroying the CNV but leaving the foveal neurosensory retina intact. Treatment modalities can be grouped into five major categories: photodynamic therapy; radiotherapy; transpupillary thermotherapy; anti-angiogenic and angiostatic agents; and surgical intervention. The present review aims to explain the rationale behind these new treatments, analyse the evidence for their safety and efficacy, determine their stage of development and indicate in which patients they are potentially useful.