Disorganization of the inner retinal layers in diabetic macular edema: systematic review / Desorganização das camadas internas da retina sem edema macular diabético: uma revisão sistemática

ABSTRACT The objective of this article was to review the disorganization of inner retinal layers as a biomarker in diabetic macular edema. A systematic search was conducted in PubMed®/MEDLINE®, Cochrane and Embase until August 2021. The keywords used were: "disorganization of inner retinal layers (DRIL)", "diabetic macular edema (DME)" and "biomarkers". No restrictions were imposed on the types of study to be included. The studies selected for eligibility were those that included the diagnosis of diabetic macular edema (center involved, resolved), that were well documented with spectral domain optical coherence tomography, that included disorganization of inner retinal layers as one of the reported alterations, with a follow-up of at least 3 months, and those in which the best corrected visual acuity was evaluated pre and post. There were no limitations regarding the type of treatment established. References of identified studies were searched for additional relevant articles. Articles not published in peer review journals were excluded. All studies were evaluated by two investigators independently. When one of them was in doubt, it was assessed by a third evaluator. A total of seven studies were included. Four were retrospective, longitudinal cohort study and three cross-sectional observational. Regarding the population studied, 61.5% were men and 38.4% were women, most of them had diabetes mellitus type 2 (85.8%). Regarding the stage of diabetes, the percentage of patients with mild nonproliferative diabetic retinopathy was 28.2%, with moderate nonproliferative diabetic retinopathy was 28.5%, with severe nonproliferative diabetic retinopathy was 15.9% and with nonproliferative diabetic retinopathy was 27.4%. In 100% of the studies, the diagnosis of diabetic macular edema in the center involved was included by spectral domain optical coherence tomography (Heidelberg). In all the studies, the presence of disorganization of inner retinal layers was recorded and its association with best corrected visual acuity was evaluated. The measurement was carried out using the LogMAR scale. In all the studies, the presence or absence of disorganization of inner retinal layers was associated with the best corrected worse/better final visual acuity using p <0.05 as a statical significance. The disorganization of inner retinal layers as a biomarker and their presence have shown to be important predictors of visual acuity in the future in patients with diabetic macular edema. Histopathological studies are required to understand its mechanism of action.

RESUMO O objetivo deste artigo foi revisar sobre a desorganização das camadas internas da retina como biomarcador no edema macular diabético. Uma busca sistemática foi realizada no PubMed®/MEDLINE®, Cochrane e Embase até agosto de 2021. As palavras-chave utilizadas foram "disorganization of inner retinal layers (DRIL)", "diabetic macular edema (DME)" e "biomarkers". Não foram impostas restrições quanto aos tipos de estudo a serem incluídos. Os estudos selecionados para elegibilidade foram aqueles que incluíram o diagnóstico de edema macular diabético (centro envolvido, resolvido), que foram bem documentados com tomografia de coerência óptica de domínio espectral, que incluíram a desorganização das camadas internas da retina como uma das alterações relatadas, com acompanhamento de pelo menos 3 meses, e aqueles em que a melhor acuidade visual corrigida foi avaliada pré e pós. Não houve limitações quanto ao tipo de tratamento estabelecido. Referências de estudos identificados foram pesquisadas para artigos relevantes adicionais. Foram excluídos os artigos não publicados em revistas de revisão por pares. Todos os estudos foram avaliados por dois investigadores de forma independente. Quando havia dúvida com algum deles, a mesma era avaliada por um terceiro avaliador. Um total de sete estudos foram incluídos. Quatro eram estudos de coorte retrospectivos longitudinais e três eram observacionais transversais. Em relação à população estudada, a proporção de homens foi de 61,5% e de mulheres, 38,4%, a maioria com diabetes mellitus tipo 2 (85,8%). Em relação ao estágio do diabetes, o percentual de pacientes com retinopatia diabética não proliferativa leve foi de 28,2%, retinopatia diabética não proliferativa moderada foi de 28,5%, de retinopatia diabética não proliferativa grave foi de 15,9% e de retinopatia diabética não proliferativa foi de 27,4%. Em 100% dos estudos, o diagnóstico de edema macular diabético no centro envolvido foi incluído pela tomografia de coerência óptica de domínio espectral (Heidelberg). Em todos os estudos, foi registrada a presença de desorganização das camadas internas da retina e avaliada sua associação com a melhor acuidade visual corrigida. A medição foi realizada usando a escala LogMAR. Em todos os estudos, a presença ou ausência de desorganização das camadas internas da retina foi associada a pior/melhor acuidade visual final melhor corrigida usando p<0,05 como significância estática. A desorganização das camadas internas da retina como biomarcador e sua presença têm se mostrado importantes como preditor da acuidade visual no futuro em pacientes com edema macular diabético. Estudos histopatológicos são necessários para entender seu mecanismo de ação.

Evidence‑based review of diabetic macular edema management: Consensus statement on Indian treatment guidelines.

The purpose of the study was to review the current evidence and design a diabetic macular edema (DME) management guideline specific for India. The published DME guidelines from different organizations and publications were weighed against the practice trends in India. This included the recently approved drugs. DME management consisted of control of diabetes and other associated systemic conditions, such as hypertension and hyperlipidemia, and specific therapy to reduce macular edema. Quantification of macular edema is precisely made with the optical coherence tomography and treatment options include retinal laser, intravitreal anti‑vascular endothelial growth factors (VEGF), and implantable dexamethasone. Specific use of these modalities depends on the presenting vision and extent of macular involvement. Invariable eyes with center‑involving macular edema benefit from intravitreal anti‑VEGF or dexamethasone implant therapy, and eyes with macular edema not involving the macula center benefit from retinal laser. The results are illustrated with adequate case studies and frequently asked questions. This guideline prepared on the current published evidence is meant as a guideline for the treating physicians.

Morphometric analysis of fovea with spectral-domain optical coherence tomography and visual outcome postsurgery for retinal detachment.

Purpose: The purpose of this study was to correlate the postoperative best-corrected visual acuity (BCVA) with spectral-domain optical coherence tomography (SD-OCT) fi ndings in fovea involving rhegmatogenous retinal detachment (RRD) surgery. Materials and Methods: Thirty eyes with preoperative fovea-involving RRD, who underwent scleral buckling (SB) (6 eyes) and pars plana vitrectomy (PPV) (19 eyes) and combined SB and PPV (5 eyes) were recruited. Patients underwent clinical examination and SD-OCT scan of fovea preoperatively and at 30 days and 90 days postoperatively. The correlations between SD-OCT fi ndings and BCVA were analyzed. Results: Inner segment/outer segment (IS/OS) junction integrity was the indicator of bett er BCVA at 30 days and 90 days (P = 0.0002 and P = 0.0003, respectively) whereas outer retinal corrugation (ORC) was related to worse BCVA at 30 days and 90 days (P = 0.001). External limiting membrane did not have a co-relation with visual outcome, but cystoid macular edema showed co-relation at 90 days (P = 0.047). All eyes of SB and 3 eyes of PPV had a minimal subfoveal fl uid at 30 days follow-up that had no eff ect on visual acuity. All retinas were att ached at fi nal follow-up. Conclusion: IS/OS junction integrity and ORC may be important predictors of postoperative visual outcome after anatomically successful RRD surgery.

Topical nepafenac 0.1% alone versus prednisolone acetate 1% as postoperative anti-inflammatory agents in small gauge vitrectomy.

Aim: To compare the effi cacy of postoperative topical nepafenac (0.1%) with prednisolone acetate (1%) as anti-infl ammatory agents in eyes undergoing Transscleral Sutureless Vitrectomy (TSV). Se􀄴 ings and Design: Prospective, double-blind, randomized, single center clinical study. Materials and Methods: Eighty eyes of 76 subjects, who underwent small gauge vitrectomy, were included in the study. The subjects who fulfi lled the inclusion criteria were randomized to either topical nepafenac only (Group 1) or prednisolone acetate only (Group 2), to be used as postoperative anti-infl ammatory agents. The subjects were reviewed on days 1, 30, and 90. Ocular and adnexal infl ammation was appropriately graded using the standardized classifi cation. Grading of ocular pain was done on the Visual Analog Scale (VAS). Statistical Analysis: The Wilcoxon rank-sum test, using two-sided analysis, was used. Results: During the follow-up, both Group 1 and Group 2 did not have a signifi cant diff erence related to the grade of the anterior chamber infl ammation (P > 0.05) or adnexal infl ammation (P > 0.05). Pain perception was less in the subjects in Group 1 as compared to subjects in Group 2, but was not statistically signifi cant (P > 0.05). Conclusion: Postoperative topical nepafenac was non-inferior to prednisolone acetate in reducing postoperative ocular infl ammation in eyes undergoing TSV.

Recent developments in retinal lasers and delivery systems.

Photocoagulation is the standard of care for several ocular disorders and in particular retinal conditions. Technology has off ered us newer lasing mediums, wavelengths and delivery systems. Patt ern scan laser in proliferative diabetic retinopathy and diabetic macular edema allows laser treatment that is less time consuming and less painful. Now, it is possible to deliver a subthreshold micropulse laser that is above the threshold of biochemical eff ect but below the threshold of a visible, destructive lesion thereby preventing collateral damage. The advent of solid-state diode yellow laser allows us to treat closer to the fovea, is more eff ective for vascular structures and off ers a more uniform eff ect in patients with light or irregular fundus pigmentation. Newer retinal photocoagulation options along with their advantages is discussed in this review.

Factors having implications on re-retinal detachments after silicone oil removal.

Aim: To investigate factors having implications on re-retinal detachments (reRD) after silicone oil removal (SOR). Materials and Methods: A retroprospective study of 412 eyes (with attached retina after vitrectomy with silicone oil for rhegmatogenous RD) which underwent SOR was conducted and were followed up for six months after SOR. They were studied for various factors like encirclage, 360° retinopexy, oil emulsification at the time of SOR, duration of oil tamponade and previous retinal surgeries prior to SOR with their implications on reRD after SOR. Results: Encirclage, 360 laser barrage, both, emulsification of oil (P=0.021, P=0.001, P=0.001, P=0.001, respectively) were associated with lower risks of reRD after SOR whereas duration of tamponade (P=0.980) was not. Conclusion: Factors like encirclage, 360 retinopexy, their combination, oil emulsification reduced the incidence of re RD after SOR whereas duration of tamponade does not have statistical significant correlation with re RD after SOR.

Adverse drug reactions to antiretroviral therapy in AIDS patients at a tertiary care hospital in India: A prospective observational study.

Objectives: To identify the adverse drug reactions (ADRs) to antiretroviral therapy (ART) and to assess their impact on treatment compliance in patients with HIV/AIDS. Materials and Methods: Two hundred and thirty-five (235) AIDS patients who received ART were monitored for ADRs over a period of 6 months. The incidence and nature of ADRs occurring with different ART regimens were recorded. We also assessed the severity, causality as well as the impact of ADRs on the patients' compliance. Results: Of 235 patients receiving ART, 90.6% patients experienced ADRs. A total of 618 ADRs involving various systems were observed. A majority were related to gastrointestinal (42.39%) and central nervous (25.57%) system. 23.1% ADRs were severe in intensity. Severe ADRs occurred in 41 out of 235 (17.4%) patients necessitating drug withdrawal. A majority of the patients (87.8%) who complained of severe ADRs received combination of stavudine, lamivudine and nevirapine. Causality assessment revealed 6.63% ADRs were probable and 93.3% ADRs were possible. Non-compliance due to ADRs was observed in 28.9% patients. Conclusions: Myriad ADRs are associated with ART which leads to poor patient compliance. With the increasing access to ART in India, it is prudent that antiretroviral drugs are used judicially with regular monitoring of ADRs.

Surgical choroidal neovascular membrane removal in the era of anti-vascular endothelial growth factor agents.

Intravitreal anti-vascular endothelial growth factor (VEGF) agents have obtained acceptance as the mainstay in the management strategy of subfoveal choroidal neovascular membranes (CNVM) due to varying etiologies. Few drawbacks include need for repeated intravitreal injections, with its adjunct risks, and the lack of a predefined treatment end point, which can cause doubts and uncertainty in the mind of the patient. Furthermore, it remains a significant financial burden for the patient. Herein we report our data of three patients who were reluctant for further re-injections of anti-VEGF agents and were therefore offered surgical removal of the CNVM by submacular surgery as an alternative treatment plan.

A comparative debate on the various anti-vascular endothelial growth factor drugs: pegaptanib sodium (Macugen), ranibizumab (Lucentis) and bevacizumab (Avastin).

Wet age-related macular degeneration and diabetic retinopathy are pathological consequences of vascular endothelial growth factor (VEGF) release as a reaction to deficiency of oxygen and nutrients in the macular cells. Conventional treatment modalities have been constrained by limited success. Convincing evidence exists that targeting VEGF signaling is a significant approach for the therapy of these ocular angiogenesis-dependent disorders. We have come a long way since the approval of the first angiogenesis inhibitors in medicine. The clinical use of these drugs has provided enormous tempo to clinical and pharmacological research. It has also significantly altered patient outcome and expectations. In the following brief, we will discuss the development and emergence of these drugs as well as the anticipated future course based on evidence.

Role of early radial optic neurotomy in central retinal vein occlusion.

PURPOSE: To determine safety, clinical and visual results, and potential complications of early radial optic neurotomy (RON) surgery in eyes with central retinal vein occlusion (CRVO), with relative afferent pupillary defect and visual acuity MATERIALS AND METHODS: This prospective, interventional case-series included 24 patients of CRVO who underwent RON within 2 months of disease onset. The preoperative examination included slitlamp biomicroscopy, fundus photography and fluorescein angiography. Foveal thickness was measured using optical coherence tomography (OCT) in the last 6 eyes only. In each case, RON was performed after informed consent. Two radial incisions were placed in the nasal quadrant of the optic disc, using a micro-vitreoretinal blade. The postoperative change in vision, clinical picture, fundus photographs, angiograms and foveal thickness by OCT were the main outcome variables studied. The Wilcoxan signed test was used to assess the results. RESULTS: Average symptom duration was 37.8 +/- 15.2 days (range 15-60 days, median: 34.5 days) and follow-up 7.7 +/- 2.1 months (range 1-12 months, median: 8 months). Visual outcome: 2 (8.33%) eyes each had fall and preservation of pre-RON visual acuity respectively. Twenty eyes (83.33%) showed increase in vision (of average 3 lines). Pre and postoperative vision ranged from 0.017-0.1 (average:0.061) and 0.017-0.667 (average: 0.17) respectively (P < 0.05). Clinical and angiographic outcome: decline in macular oedema, decreased or resolved intraretinal haemorrhages, resolution of venous dilatation and disc oedema could be appreciated in all cases. Foveal thickness: average pre and postoperative foveal thickness was 834.17 microm and 556.17 microm respectively (P < 0.05) in the 6 eyes where it was measured before and after RON. One eye developed retinal-detachment. CONCLUSION: Radial optic neurotomy is better than the natural course in eyes with CRVO, with vision < 6/60.

Juvenile rhegmatogenous retinal detachment.

PURPOSE: To review the clinical features, evaluate visual, and anatomical outcomes and potential complications following surgery for rhegmatogenous retinal detachment (RRD) in juveniles. METHODS: Retrospective, consecutive case series of children and young adults (birth through 18 years) who underwent surgerys for RRD between February 1999 and January 2002. RESULTS: The authors reviewed a consecutive series of 111 eyes of 105 juveniles [86 (77.47%) eyes belonged to male and 25 (22.52%) to female subjects] operated for RRD. The mean age of patients was 13.62 years. Bilateral retinal detachment was present in 12 (10.8%); 51 (46%) patients had some form of bilateral ocular pathology at initial presentation. The two most common aetiologies were non-penetrating trauma (45.04%) and myopia (41.44%). Decreased vision was the most frequent symptom. The mean duration of symptoms was 165.36 days. The commonest retinal break was a retinal hole (34.23%). Late diagnosis was common, evidenced by high frequency of macular detachment (97.29%) and proliferative vitreoretinopathy (PVR) (45.94%) at initial presentation. The most commonly performed primary surgery was scleral buckle (61.26%). The average postoperative follow-up after the first procedure was 10 months (range 8-19 months). Final retinal reattachment was accomplished in 78.37% (87/111) with a mean of 1.29 surgeries per eye. Improvement, no change and decline in vision was seen in 50 (48%), 32 (31%) and 22 (21%) eyes respectively. CONCLUSION: Non-penetrating injury and myopia were the most common cause for RRD in juveniles. Fellow eyes commonly had vision-threatening abnormalities. Final anatomical and visual recovery rates were encouraging despite late initial presentation and high rates of macular detachment, and PVR at initial presentation.

Transpupillary thermotherapy for treatment of choroidal neovascularization secondary to age-related macular degeneration in Indian eyes.

AIM: To evaluate the efficacy of transpupillary thermotherapy (TTT) for treatment of subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD), and to define accurate power settings for this procedure in Indian eyes. METHODS: A prospective, nonrandomised study of 160 eyes of 144 patients with subfoveal CNV. The laser settings included 2 mm spot and 300 mw power or 3 mm spot and 400-600 mw power. Two separate 3 mm spots were used in larger lesions. The treatment was given for 60 seconds at each point. RESULTS: Ninety-nine eyes had classic membranes and 61 eyes had occult membranes. Following treatment, 79 of 99 (79.8%) classic and 52 of 61 (85%) occult membranes regressed. Visual improvement (> or = 2 lines) was seen in 29 (29.3%) eyes and 12 (19.6%) eyes; visual stabilisation (1 line) in 39 (39.4%) eyes, and 35 (57.4%) eyes; and reduction of vision (< or = 2 lines) in 31 (31.3%) eyes and 14 (22.9%) eyes with classic and occult membranes respectively. Mean follow-up was 12 months. One patient suffered inadvertant foveal burn. CONCLUSION: TTT is effective in the management of subfoveal membranes in Indian eyes. They respond to lower energy levels compared to the Caucasian eyes.