Deciphering the connection between microvascular damage and neurodegeneration in early diabetic retinopathy

Diabetic retinopathy (DR), a common diabetes complication leading to vision loss, presents early clinical signs linked to retinal vasculature damage, affecting the neural retina at advanced stages. However, vascular changes and potential effects on neural cells before clinical diagnosis of DR are less well understood. To study the earliest stages of DR we performed histological phenotyping and quantitative analysis on postmortem retinas from 10 donors with diabetes and without signs of DR (such as microaneurysms and haemorrhages), plus 3 controls and 1 DR case, focusing on capillary loss in the deeper (DVP) and superficial vascular plexuses (SVP) and neural retina effects. The advanced DR case exhibited profound vascular and neural damage, whereas the ten randomly selected donors with diabetes appeared superficially normal. The SVP was indistinguishable from the controls. In contrast, over half of the retinas from donors with diabetes showed capillary dropout in the DVP and increased capillary diameter. However, we could not detect any localised neural cell loss in the vicinity of dropout capillaries. Instead, we observed a subtle pan-retinal loss of inner nuclear layer (INL) cells in all diabetes cases (p<0.05), independent of microvascular damage. In conclusion, our findings demonstrate a novel histological biomarker for early-stage diabetes-related damage in human postmortem retina, common in people with diabetes before clinical DR diagnosis. Furthermore, the mismatch between capillary dropout and neural loss questions the notion of microvascular loss directly causing neurodegeneration at the earliest stages of DR, so diabetes may affect the two readouts independently

Safety and efficacy of intravitreal preservative-free triamcinolone acetonide (Triesence) for macular edema

Purpose: To evaluate the efficacy and safety of preservative-free triamcinolone acetonide (Triesence) for the treatment of macular edema. Methods: A retrospective study was conducted on patients who attended a tertiary retinal clinic from June 2009 to July 2012 with macular edema due to various causes. Patients who received at least 1 intravitreal Triesence injection and completed 6 months of follow-up were recruited. Data, including best-corrected Snellen visual acuity, central macular thickness (CMT), intraocular pressure (IOP), and adverse events (AEs), were collected at baseline, week 1, month 1, month 3, and month 6 after initiation of treatment. Snellen visual acuity was converted to visual acuity score (VAS) for statistical analysis using paired t-tests and linear regression. Results: One hundred two eyes from 102 patients were included in the study. Mean VAS was significantly improved at all follow-up time points compared to baseline (P≤0.002), with highest mean gain at month 1 (6.1±8.9 letters). Mean CMT decreased significantly at all follow-up points compared to baseline (P≤0.0005), with the greatest reduction at week 1 (146.6±109.4 μm). A total of 22 AEs were observed, and IOP elevation was the most common AE related to Triesence treatment (17/22, 77.3%). No sterile or infectious endophthalmitis was observed. Conclusion: Intravitreal Triesence improves visual acuity and reduces macular thickness in eyes with macular edema from various causes. Treatment-associated IOP elevation was manageable with antiglaucoma medications. There were no serious vision-threatening complications associated with intravitreal Triesence therapy during the study period.7 page(s

Efficacy and safety of multiple intravitreal triamcinolone injections for refractory diabetic macular oedema

Aim: The efficacy and safety of repeated injections of intravitreal triamcinolone (IVTA) for diabetic macular oedema is unclear, with results of previous reports conflicting. Methods: This is a prospective, observational case series of 27 eyes receiving IVTA for diabetic macular oedema. LogMAR visual acuity (VA) and central macular thickness (CMT) were measured at baseline and in 3 to 6 monthly intervals for up to 24 months, then correlated with the number of IVTA injections given. Results: One IVTA injection was required in 6 (18%) eyes, 2 in 8 (24%) eyes, 3 in 13 (39%) eyes and 4–5 in 6 (18%) eyes. VA improved in all patients, but neither the final improvement in VA nor the absolute improvement in CMT from baseline to 24 months correlated with the number of injections received (p = 0.44 and 0.84, respectively). Cataract surgery was more frequent in eyes receiving more injections (p = 0.01). Conclusions: This study suggests that repeated injections of IVTA continue to be as effective as the first over a 2‐year period. The probability of cataract surgery increases with an increasing number of injections

Triamcinolone-induced cataract in eyes with diabetic macular oedema: 3-year prospective data from a randomized clinical trial

Purpose: To describe the 3-year risk of cataract after intravitreal triamcinolone (IVTA) injections for diabetic macular oedema and the outcomes of cataract surgery. Methods: Prospective data from a randomized clinical trial were analysed. At baseline, 27 phakic eyes with diabetic macular oedema were randomized to receive IVTA and 25 to receive sham injection. After 2 years, initial sham-treated eyes were eligible to receive IVTA as the study became open label for the third year. The cumulative incidence of cataract surgery was the primary outcome of the study. Other outcomes assessed included progression of cataract, best-corrected logarithm of the minimal angle of resolution visual acuity before and after surgery and central macular thickness. Results: Over the 3 years of the study, 15/27 (56%) phakic eyes in the IVTA treated group underwent cataract surgery as compared with 2/25 (8%) initial sham-treated eyes (P 15 letters. In the IVTA-treated group, 10/15 (67%) eyes that had three or more injections had progression of posterior subcapsular cataract by 2 grades as compared with only 2/12 (17%) eyes that had fewer than three injections (P = 0.009). Conclusions: Over half of the eyes receiving IVTA injections for diabetic macular oedema required cataract surgery within 3 years. In eyes with three or more IVTA injections, two-thirds had progression of posterior subcapsular cataract. Visual outcomes after cataract surgery were generally good, although a small proportion of eyes lost greater than 15 letters over the course of the study

Intraocular pressure rise is predictive of vision improvement after intravitreal triamcinolone acetonide for diabetic macular oedema: a retrospective analysis of data from a randomised controlled trial

BACKGROUND: Intravitreal triamcinolone acetonide (IVTA) is an effective treatment for recalcitrant diabetic macular oedema (DMO). It has been shown to improve vision with benefits persisting up to five years. The most common initial side effect of IVTA treatment is rise in intraocular pressure, occurring in approximately 50% of patients within the first 6 months of treatment. We evaluated whether there is a correlation between the development of intraocular pressure rise and improvement in vision. METHODS: Analysis of individual data from 33 eyes of 33 participants treated with IVTA for DMO from a prospective, randomised, double-masked, placebo controlled trial. The degree of intraocular pressure (IOP) rise was correlated with improvement in best-corrected visual acuity (BCVA) at 1 and 6 months. RESULTS: The proportion of eyes gaining 5 or more logMAR letters was higher in eyes with greater IOP rise (p = 0.044). Better absolute improvement in BCVA at 6 months (p = 0.045) was also found in eyes with greater IOP rise. Regression analyses revealed a correlation between IOP rise of 10 or more mmHg and absolute BCVA improvement at 6 months (odds ratio 1.22, 95% confidence interval 1.01-1.48, p = 0.039), but not at 1 month. CONCLUSIONS: IOP rise and vision improvement appear to be correlated following IVTA for DMO, suggesting that the mechanisms that cause both may be linked. TRIAL REGISTRATION: Clinical trials.gov NCT00167518, September 5, 2005

Intravitreal ranibizumab for neovascular age-related macular degeneration in clinical practice : five-year treatment outcomes

Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are the established standard of care for neovascular age-related macular degeneration (nAMD). However, data on long-term outcomes of this therapy are limited. The purpose of this study was to assess the visual and anatomical outcomes and safety profile of intravitreal ranibizumab in treating nAMD over a period of five years. Methods: 208 patients (208 eyes) were included in this retrospective case series study. Intervention was an "as-needed" treatment model. Visual acuity (VA), central macular thickness (CMT), ophthalmic examination, and adverse events (AEs) were assessed in each visit. Snellen VA was converted to Early Treatment Diabetic Retinopathy Study letters for analysis. Results: The average VA improved by 1.9 letters after one year (p = 0.017), and decreased by 2.4 letters over five years of treatment (p = 0.043). At the end of year five, 11.1 % of patients (23/208) had improved VA by more than 15 letters and 68.8 % (143/208) had VA improvement or loss less than or equal to 15 letters, while 20.2 % of patients (42/208) had a loss of more than 15 letters. Patients with VA of less than 35 letters at baseline showed significant VA improvement after five years of treatment. There was a positive relationship between injection numbers and VA improvement over the five-year period, after adjusting for age and baseline VA (p < 0.0005). Mean CMT decreased by 28.3 μm (p < 0.0005) over five years. Ocular AEs, serious adverse events (SAEs), and systemic SAEs occurred in 4.6 %, 0.48 %, and 2 % of patients, respectively, during the follow-up period. Conclusions: The use of intravitreal ranibizumab in an as-needed treatment regimen over a five-year period was effective in maintaining vision in patients with nAMD and in reducing macular thickness, with a relatively low rate of adverse and serious adverse events.9 page(s

Ultrastructural and clinical evidence of subretinal debris accumulation in type 2 macular telangiectasia

Aims: To describe subretinal debris found on ultrastructural examination in an eye with macular telangiectasia (MacTel) type 2 and on optical coherence tomography (OCT) in a subset of patients with MacTel type 2. Methods: Blocks from the mid-periphery and temporal perifovea of an eye with clinically documented MacTel type 2 were examined with electron microscopy (EM). Cases came from the Sydney centre of the MacTel project and the practices of the authors. Results: On EM examination, subretinal debris was found in the perifovea with accumulation of degenerate photoreceptor elements in the subretinal space. Despite the substantial subretinal debris, there was minimal retinal pigment epithelial (RPE) reaction. Focal defects were seen in the inner limiting membrane in the perifovea. Of the 65 Sydney MacTel project participants, three (5%) had prominent yellow material at the fovea. OCT revealed smooth mounds between the RPE and the ellipsoid region. The material was hyperautofluorescent. Conclusions: This study suggests that subretinal accumulation of photoreceptor debris may be a feature of MacTel type 2. Ultrastructural and OCT evidence of disease beyond the vasculature, involving photoreceptors and Muller cells, is presented.6 page(s

Groups for TGF-β1 signaling pathway experiments.

<p>Groups for TGF-β1 signaling pathway experiments.</p