Refractive Error and Retinopathy Outcomes in Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study.

PURPOSE: To determine the relationship between refractive error and diabetic retinopathy (DR). DESIGN: Clinical trial. PARTICIPANTS: Type I diabetes individuals with serial refractive error and DR stage measurements over 30 years in the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study. METHODS: Stage of DR was measured every 6 months from standard fundus photographs, and refractive error was measured annually during the 6.5 years of DCCT; then, both were staggered every fourth year during EDIC with the full cohort measured at EDIC years 4 and 10. Outcomes of DR were 2- or 3-step progression, presence of proliferative DR (PDR), clinically significant macular edema (CSME), diabetic macular edema (DME), or ocular surgery. Myopia, emmetropia, and hyperopia were defined as a spherical equivalent of ≤-0.5, >-0.5 and <0.5, and ≥0.5, respectively. MAIN OUTCOME MEASURES: For each outcome separately, Cox proportional hazard (PH) models assessed the association between the refractive error status and the subsequent risk of that outcome, both without and with adjustment for potential risk factors. RESULTS: Hyperopia was associated with a higher risk of 2-step progression (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.05-1.59), 3-step progression (HR, 1.35; 95% CI, 1.05-1.73), and PDR (HR, 1.40; 95% CI, 1.02-1.92) compared with emmetropia in unadjusted models. These associations remained significant after adjustment for DCCT treatment group, cohort, age, sex, smoking, duration of diabetes, systolic and diastolic blood pressures, pulse, low-density lipoprotein, high-density lipoprotein, triglycerides, albumin excretion rate, and DCCT/EDIC mean updated hemoglobin A1c (HbA1c) (2-step progression: HR, 1.28; 95% CI, 1.03-1.58; 3-step progression: HR, 1.30; 95% CI, 1.00-1.68; PDR: HR, 1.38; 95% CI, 1.00-1.90). Myopia was not associated with any of the 5 DR outcomes in the unadjusted models and only marginally associated with 2-step progression (HR, 1.11; 95% CI, 1.00-1.24) in the adjusted models. CONCLUSIONS: Myopia is not associated with DR progression risk. Hyperopia is an independent risk factor for 2-step and 3-step DR progression and PDR.

Plate-Adherent Nanosubstrate for Improved ELISA of Small Molecules: A Proof of Concept Study.

Enzyme-linked immunosorbent assay (ELISA) is a widely used technique for detecting and quantifying target analytes in clinical and research laboratories. One of the main drawbacks of ELISA is the involvement of multiple washing steps that desorbs the capture antigen/antibody off the polystyrene plate, thereby producing inconsistent and erroneous data. To overcome the problem of desorption, we hypothesized that gelatin nanoparticles (GelNP) could serve as a "plate-adherent" substrate to irreversibly adhere the capture antigen/antibody of interest. We tested our hypothesis using GelNP-based substrate (Gel-BSA-OHG) to adhere 8-hydroxy-2'-deoxyguanosine (8-OHdG) to the polystyrene plate and assayed this molecule using the ELISA technique. The stability and ELISA performance of Gel-BSA-OHG was evaluated in comparison to the conventional substrate (BSA-OHG). Importantly, the Gel-BSA-OHG substrate was found to be more wash-resistant and consequently resulted in improved sensitivity, accuracy, and precision in the ELISA analysis of 8-OHdG. Finally, the scope of Gel-BSA-OHG substrate-based ELISA for clinical application was demonstrated by validating its ability to detect 8-OHdG in an artificial urine sample with high specificity.

NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy.

Diabetic retinopathy (DR) is an ocular complication of diabetes mellitus (DM). International Diabetic Federations (IDF) estimates up to 629 million people with DM by the year 2045 worldwide. Nearly 50% of DM patients will show evidence of diabetic-related eye problems. Therapeutic interventions for DR are limited and mostly involve surgical intervention at the late-stages of the disease. The lack of early-stage diagnostic tools and therapies, especially in DR, demands a better understanding of the biological processes involved in the etiology of disease progression. The recent surge in literature associated with NOD-like receptors (NLRs) has gained massive attraction due to their involvement in mediating the innate immune response and perpetuating inflammatory pathways, a central phenomenon found in the pathogenesis of ocular diseases including DR. The NLR family of receptors are expressed in different eye tissues during pathological conditions suggesting their potential roles in dry eye, ocular infection, retinal ischemia, cataract, glaucoma, age-related macular degeneration (AMD), diabetic macular edema (DME) and DR. Our group is interested in studying the critical early components involved in the immune cell infiltration and inflammatory pathways involved in the progression of DR. Recently, we reported that NLRP3 inflammasome might play a pivotal role in the pathogenesis of DR. This comprehensive review summarizes the findings of NLRs expression in the ocular tissues with special emphasis on its presence in the retinal microglia and DR pathogenesis.

Characterization of a functionally active primary microglial cell culture from the pig retina.

Retinal inflammation is an integral component of many retinal diseases including diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinopathy of prematurity (ROP). Inflammation is commonly initiated and perpetuated by myeloid-derived immune cells. In the retina, microglial cells are resident macrophages with myeloid origins, which acts as the first responders involved in the innate immune system. To understand the disease pathogenesis, the use of isolated retinal cell culture model is vital for the examination of multiple cellular responses to injury or trauma. The pig retina resembles human retina in terms of tissue architecture, vasculature, and topography. Additionally, it is a better model than the rodent retina because of the presence of the pseudomacula. In the present study, we sought to establish and characterize pig retinal primary microglial cell (pMicroglia) culture. We used pig eyes from the local abattoir and optimized pMicroglia cultures using multiple cell culture conditions and methods. The best results were obtained by seeding cells in DMEM-high glucose media for 18 days followed by shaking of the culture plate. The resulting pMicroglia were characterized by cellular morphology, phenotype, and immunostaining with Iba-1, CD68, P2Y12, CD163, CD14, and Isolectin GS-IB4. Generated pMicroglia were found functionally active in phagocytosis assay and responsive to lipopolysaccharides (LPS) in dose-dependent production of IL-1ß. Furthermore, they showed increased secretion of pro-inflammatory cytokines with LPS treatment. Thus, we report a novel and reproducible method for the isolation of primary microglial cells from pig eyes, which may be useful for studying retinal diseases.

Screening eye exams in youth with type 1 diabetes under 18 years of age: Once may be enough?

Case series and registry data suggest that diabetic retinopathy requiring treatment is rare in youth with type 1 diabetes (T1D) prior to 18 years of age. We evaluated this question in the standardized clinical trial setting by retrospectively reviewing diabetic retinopathy examinations from participants in the Diabetes Control and Complications Trial (DCCT) who were 13 to <18 years of age at randomization. Standardized stereoscopic 7-field fundus photographs were obtained every 6 months during DCCT (1983-1993). Photographs were graded centrally using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Transitions in diabetic retinopathy status over time were described. A total of 195 participants with median baseline glycated hemoglobin (HbA1c) of 9.3% (103 in the conventional and 92 in the intensive treatment groups) had an average of 5.3 diabetic retinopathy assessments during 2.3 years of follow-up (range 1-11) while under 18 years of age during the DCCT. No participant developed severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy and only one participant (in the intensive group) reached clinically significant macular edema (CSME) while less than 18 years of age. In this incident case, baseline characteristics included diabetes duration 9.3 years, HbA1c 10.3%, LDL 131 mg/dL, and mild non-proliferative diabetic retinopathy (35/35 ETDRS scale); CSME resolved without treatment. Similar analyses using age cut-offs of <19, 20, or 21 years showed a slight rise in diabetic retinopathy requiring treatment over late adolescence. Clinical trial evidence suggests that frequent eye exams may not be universally necessary in youth <18 years of age with T1D.

Vitrectomy as a Risk Factor for Complicated Cataract Surgery.

A retrospective review of 98 cases of complicated cataract surgery and/or delayed intraocular lens (IOL) dislocation examined the relationship between vitrectomy and cataract surgery complications. Nine (9.2%) of the 98 patients had a history of vitrectomy, before or after cataract surgery, and each had complicated cataract surgery. Six patients who underwent vitrectomy before cataract surgery experienced intraoperative complications. Three patients in whom vitrectomy was performed after uneventful cataract surgery subsequently had delayed IOL dislocation.

Surgical management of rhegmatogenous retinal detachment: a meta-analysis of randomized controlled trials.

PURPOSE: To examine possible differences in clinical outcomes between pars plana vitrectomy (PPV) and scleral buckling (SB) for uncomplicated rhegmatogenous retinal detachment (RRD). DESIGN: Meta-analysis. PARTICIPANTS: Adult patients with uncomplicated RRD from previously reported randomized controlled trials of PPV and SB. METHODS: A comprehensive literature search using the Cochrane Collaboration methodology to identify randomized controlled trials comparing PPV with SB for uncomplicated RRD. MAIN OUTCOME MEASURES: Analysis was divided into phakic and pseudophakic/aphakic patients. Primary outcome parameters included proportion of primary reattachment and difference of means of best-corrected visual acuity (BCVA) at 6 months or more between the PPV and SB groups. Secondary outcome parameters included the proportion of secondary reattachment and complications between the PPV and SB groups. RESULTS: Seven studies were identified and analyzed for comparing PPV (636 eyes) with SB (670 eyes) for uncomplicated RRD. In the phakic group, there were no significant differences in the proportion of primary reattachments (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.69-1.46) or secondary reattachments (OR, 0.99; 95% CI, 0.34-2.87) between the PPV and SB groups. Meta-analysis showed a statistically significant difference in the logarithm of the minimum angle of resolution (logMAR) BCVA at 6 months between the PPV-treated and SB-treated phakic eyes (mean deviation, 0.14; 95% CI, 0.06-0.21; P<0.0004). In the pseudophakic/aphakic group, there were no significant differences in the proportion of primary reattachments (OR, 1.46; 95% CI, 0.79-2.71) or logMAR BCVA at 6 months between the PPV and SB groups (mean deviation, -0.03; 95% CI, -0.10 to 0.04). A statistically significant difference was noted in the proportion of secondary reattachments (OR, 2.08; 95% CI, 1.08-4.03; P = 0.03) between the PPV and SB groups in pseudophakic/aphakic eyes. Meta-analysis showed a statistically significant rate of cataract progression in the PPV group (OR, 4.11; 95% CI, 2.70-6.25; P<0.00001). CONCLUSIONS: There were no significant differences in the proportions of primary reattachment in the PPV and SB groups in phakic eyes. The SB-treated phakic eyes had better postoperative BCVA at 6 months or more. This is most likely related to higher rates of cataract progression in PPV-treated phakic eyes. There were no significant differences in proportions of primary reattachment and postoperative BCVA at 6 months or more in pseudophakic/aphakic eyes.

Eye on statins: A comprehensive review.

Over the last 25 years, statins have demonstrated their safety from an ophthalmologic standpoint. Studies relating statin to cataract formation are insufficient to alter the usual and customary prescription of statins. If there is an association between statins and cataracts, it is weak and clinically insignificant. Prospective studies have not demonstrated a benefit of adding statin therapy in patients with age-related macular degeneration (ARMD), but these studies have not been adequately powered to detect moderate differences. A subset of patients with persistently elevated lipids despite taking statins may be at higher risk of developing wet ARMD. The use of statins for the prevention and/ or treatment of glaucoma patients warrants further prospective study. There is a possibility that statins may unmask or exacerbate myasthenia gravis.

Retinopathy During the First 5 Years of Type 1 Diabetes and Subsequent Risk of Advanced Retinopathy.

OBJECTIVE: To determine whether individuals with type 1 diabetes (T1D) who develop any retinopathy at any time prior to 5 years of diabetes duration have an increased subsequent risk for further progression of retinopathy or onset of proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), diabetes-related retinal photocoagulation, or anti-vascular endothelial growth factor injections. Additionally, to determine the influence of HbA1c and other risk factors in these individuals. RESEARCH DESIGN AND METHODS: Diabetic retinopathy (DR) was assessed longitudinally using standardized stereoscopic seven-field fundus photography at time intervals of 6 months to 4 years. Early-onset DR (EDR) was defined as onset prior to 5 years of T1D duration. Cox models assessed the associations of EDR with subsequent risk of outcomes. RESULTS: In unadjusted models, individuals with EDR (n = 484) had an increased subsequent risk of PDR (hazard ratio [HR] 1.51 [95% CI 1.12, 2.02], P = 0.006), CSME (HR 1.44 [1.10, 1.88], P = 0.008), and diabetes-related retinal photocoagulation (HR 1.48 [1.12, 1.96], P = 0.006) compared with individuals without EDR (n = 369). These associations remained significant when adjusted for HbA1c, but only the association with PDR remained significant after adjustment for age, duration of T1D, HbA1c, sex, systolic/diastolic blood pressure, pulse, use of ACE inhibitors, albumin excretion rate, and estimated glomerular filtration rate (HR 1.47 [95% CI 1.04, 2.06], P = 0.028). CONCLUSIONS: These data suggest that individuals with any sign of retinopathy within the first 5 years of T1D onset may be at higher risk of long-term development of advanced DR, especially PDR. Identification of early-onset DR may influence prognosis and help guide therapeutic management to reduce the risk of future visual loss in these individuals.

Diabetic Retinopathy Screening Using a Gold Nanoparticle-Based Paper Strip Assay for the At-Home Detection of the Urinary Biomarker 8-Hydroxy-2'-Deoxyguanosine.

PURPOSE: We sought to assess a smartphone-based, gold nanoparticle-based colorimetric lateral flow immunoassay paper sensor for quantifying urine 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a biomarker for diabetic retinopathy (DR) screening. METHODS: Paper strips incorporate gold nanoparticle-8-OHdG antibody conjugates that produce color changes that are proportional to urine 8-OHdG and that are discernible on a smartphone camera photograph. Paper strip accuracy, precision, and stability studies were performed with 8-OHdG solutions of varying concentrations. Urine was collected from 97 patients with diabetes who were receiving DR screening examinations, including 7-field fundus photographs. DR was graded by standard methods as either low risk (no or mild DR) or high risk (moderate or severe DR). Paper sensor assays were performed on urine samples from patients and 8-OHdG values were correlated with DR grades. The differences in 8-OHdG values between the low- and high-risk groups were analyzed for outliers to identify the threshold 8-OHdG value that would minimize false-negative results. RESULTS: Lateral flow immunoassay paper strips quantitatively measure 8-OHdG and were found to be accurate, precise, and stable. Average urine 8-OHdG concentrations in study patients were 22 ± 10 ng/mg of creatinine in the low-risk group and 55 ± 11 ng/mg of creatinine in the high-risk group. Screening cutoff values of 8-OHdG >50 ng/mg of creatinine or urine creatinine >1.5 mg minimized screen failures, with 91% sensitivity and 81% specificity. CONCLUSIONS: Urinary 8-OHdG is a useful biomarker to screen DR. Quantitative 8-OHdG detection with the lateral flow immunoassay paper sensor and smartphone camera demonstrates its potential in DR screening. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Funduscopic and angiographic appearance in the neuronal ceroid lipofuscinoses.

PURPOSE: To characterize the retinal features of neuronal ceroid lipofuscinoses (NCLs) and to determine if retinal abnormalities are detectable in carriers of these autosomal recessively inherited diseases. METHODS: Carriers of the NCLs and their affected children underwent ophthalmic examination including color fundus photography in all patients and fluorescein angiography in selected patients. Twenty-nine patients with NCL were examined and photographed: 3 with infantile form, 2 with late-infantile form, and 24 with juvenile form. Fourteen patients underwent fluorescein angiography. RESULTS: Infantile and late-infantile retinal findings include fine retinal pigment epithelium pigment atrophy with no bone spicule changes and disk pallor. Juvenile retinal findings include macular retinal pigment epithelium atrophy and pigment stippling (>50%), epiretinal membrane (33%), bull's eye maculopathy (25%), and peripheral bone spicules (46%) and variable disk pallor. Fluorescein angiography of juvenile patients demonstrated diffuse retinal pigment epithelium atrophy with stippled hyperfluorescence (93%). Heterozygous NCL carriers had no identifying retinal abnormalities. CONCLUSION: Significant variability exists in the retinal appearance of the NCLs, but, in general, ophthalmoscopy and fluorescein angiography distinguish these patients from other more common blinding disorders of childhood such as retinitis pigmentosa and Stargardt disease. Examining retinas of parents of affected children does not aid in the diagnosis of NCL.

Correlation between systemic S100A8 and S100A9 levels and severity of diabetic retinopathy in patients with type 2 diabetes mellitus.

AIMS: S100A8 and S100A9 are myeloid-related damage-associated molecular patterns (DAMPs) primarily involved in the modulation of innate immune response to cellular injury. This study evaluated the correlation between circulating concentrations of S100A8 and S100A9 proteins with the severity of diabetic retinopathy (DR) in patients with type 2 diabetes (T2DM). METHODS: T2DM patients with HbA1c levels >7%, fasting blood glucose >126 mg/dl and history of diabetes were included in this study. DR severity was graded based on ETDRS and Gloucestershire classifications. Plasma samples were evaluated for S100A8 and S100A9 levels using ELISA. RESULTS: In this comparative study, DR patients (n = 89) had increased plasma S100A8 and S100A9 proteins compared to age-matched T2DM controls (n = 28), which was directly related to the severity of DR. Female DR subjects had increased S100A8 expression compared to their male counterparts. Substantial retention of S100A8 and S100A9 production was seen in DR patients above 50 years of age. Duration of T2DM was not found to affect protein levels, however T2DM onset at >50 years old significantly increased S100A8 and S100A9 concentrations. CONCLUSIONS: Our findings suggest that systemic circulation levels of S100A8 and S100A9 are correlated with the progression of DR in T2DM patients, indicating their potential role in DR pathogenesis.

Risk Factors for Retinopathy in Type 1 Diabetes: The DCCT/EDIC Study.

OBJECTIVE: The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy reduced the development and progression of retinopathy in type 1 diabetes (T1D) compared with conventional therapy. The Epidemiology of Diabetes Interventions and Complications (EDIC) study observational follow-up showed persistent benefits. In addition to glycemia, we now examine other potential retinopathy risk factors (modifiable and nonmodifiable) over more than 30 years of follow-up in DCCT/EDIC. RESEARCH DESIGN AND METHODS: The retinopathy outcomes were proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), and ocular surgery. The survival (event-free) probability was estimated using the Kaplan-Meier method. Cox proportional hazards models assessed the association between risk factors and subsequent risk of retinopathy. Both forward- and backward-selection approaches determined the multivariable models. RESULTS: Rate of ocular events per 1,000 person-years was 12 for PDR, 14.5 for CSME, and 7.6 for ocular surgeries. Approximately 65%, 60%, and 70% of participants remained free of PDR, CSME, and ocular surgery, respectively. The greatest risk factors for PDR in descending order were higher mean HbA1c, longer duration of T1D, elevated albumin excretion rate (AER), and higher mean diastolic blood pressure (DBP). For CSME, risk factors, in descending order, were higher mean HbA1c, longer duration of T1D, and greater age and DBP and, for ocular surgeries, were higher mean HbA1c, older age, and longer duration of T1D. CONCLUSIONS: Mean HbA1c was the strongest risk factor for the progression of retinopathy. Although glycemic control is important, elevated AER and DBP were other modifiable risk factors associated with the progression of retinopathy.

Young Ossabaw Pigs Fed a Western Diet Exhibit Early Signs of Diabetic Retinopathy.

Purpose: Recent clinical data suggest an increasing prevalence of obesity and type 2 diabetes in adolescents, placing them at high risk of developing diabetic retinopathy during adult working years. The present study was designed to characterize the early retinal and microvascular alterations in young Ossabaw pigs fed a Western diet, described as a model of metabolic syndrome genetically predisposed to type 2 diabetes. Methods: Four-month-old Ossabaw miniature pigs were divided into two groups, lean and diet-induced obesity. Obese pigs were fed a Western diet with high-fat/high-fructose corn syrup/high-choleric content for 10 weeks. Blood and retina were collected for biochemical profiling, trypsin digest, flatmounts, Fluoro-Jade C staining, electron microscopy, quantitative PCR, immunohistochemistry, and Western blots. Results: Young Ossabaw pigs had elevated fasting blood glucose after feeding on a Western diet for 10 weeks. Their retina showed disrupted cellular architecture across neural layers, with numerous large vacuoles seen in cell bodies of the inner nuclear layer. Microvessels in the obese animals exhibited thickened basement membrane, along with pericyte ghosts and acellular capillaries. The pericyte to endothelial ratio decreased significantly. Retina flatmounts from obese pigs displayed reduced capillary density, numerous terminal capillary loops, and string vessels, which stained collagen IV but not isolectin IB4. Quantitative PCR and Western blots showed significantly high levels of basement membrane proteins collagen IV and fibronectin in obese pigs. Conclusions: This is the first study to describe the ultrastructural neuronal and vascular changes in the retina of young Ossabaw pigs fed a Western diet, simulating early signs of diabetic retinopathy pathogenesis.

Intravitreal triamcinolone acetonide concentration after subtenon injection.

PURPOSE: To determine concentration of intravitreal triamcinolone after subtenon injection. DESIGN: Prospective series of vitrectomy candidates and laboratory investigation. METHODS: Twenty eyes of 20 patients received subtenon injections of triamcinolone acetonide, 40 mg, before vitrectomy surgery. Exclusion criteria included previous history of vitrectomy, triamcinolone injection, and retinal detachment. Posterior subtenon injections were performed using the standard technique. Undiluted vitreous specimens were obtained at the time of vitrectomy, which was performed from one to 29 days after subtenon injection. Intravitreal triamcinolone concentration was determined by high-performance liquid chromatography. RESULTS: No complications were associated with subtenon injections. Intravitreal triamcinolone concentrations varied considerably, from zero in five eyes to a high of 4.94 microg/ml. CONCLUSIONS: Intravitreal triamcinolone concentrations vary considerably after subtenon injection. The findings indicate that subtenon injection can be a method for administering intravitreal triamcinolone acetonide that is comparable, in some cases, to the levels achieved after intravitreal injection.

Bruch's membrane abnormalities in dome-shaped and mushroom-shaped choroidal melanomas.

INTRODUCTION: Mushroom-shaped choroidal melanoma is known to be associated with breaks in Bruch's membrane and is more likely to develop when Bruch's membrane is diseased. The study's goal is to determine if diseases causing breaks in Bruch's membrane predispose a choroidal melanoma to develop into a mushroom-shaped melanoma. MATERIALS AND METHODS: A retrospective review of cases of choroidal melanoma seen at our institution was carried out to determine if mushroom-shaped melanomas are more common than dome-shaped tumours in patients with macular abnormalities involving a loss of Bruch's membrane integrity. Forty-nine eyes of 48 patients were included in this retrospective study. A dome-shaped or mushroom-shaped configuration was assigned to each tumour. Macular degeneration, macular drusen, retinal pigment epithelial (RPE) stippling, macular oedema, choroidal neovascularisation (CNV), angioid streaks, disciform scars, lacquer cracks, and myopia greater than -3.00 D, were considered to constitute evidence of potential Bruch's membrane breaks and were determined in both eyes. A chi-square evaluation was used to compare the proportion of eyes with macular abnormalities in the 2 tumour configuration groups. RESULTS: The tumour was dome-shaped in 40 eyes (82%) and mushroom-shaped in 9 eyes (18%). Macular abnormalities, indicative of loss of Bruch's membrane integrity, were seen in 21 (53%) of 40 eyes with dome-shaped melanomas and 5 (56%) of 9 eyes with mushroom-shaped melanomas. The proportion of eyes with macular abnormalities was not statistically different between the dome-shaped and mushroom-shaped tumours, as assessed by chi-square analysis (P = 0.87). CONCLUSIONS: Bruch's membrane disease does not influence the differentiation of choroidal melanoma into mushroom-shaped or dome-shaped tumour growth patterns.

Electroretinographic effects of an intravitreal injection of triamcinolone in rabbit retina.

OBJECTIVE: To investigate the clinical, histologic, and electroretinographic effects of intravitreal injection of triamcinolone acetonide suspension in the rabbit retina. METHODS: Three groups of 6 rabbits each received intravitreal injections. Group 1 received 4 mg of triamcinolone acetonide, group 2 received an equal volume (0.1 mL) of the corticosteroid supernatant, and group 3 received 4 mg of triamcinolone acetonide with the supernatant replaced with balanced salt solution. Uninjected left eyes served as controls. Electroretinograms were obtained at baseline and at 3 to 4 and 6 to 7 days after injection of triamcinolone. Enucleated eyes were examined histologically. RESULTS: Ocular examination revealed no differences among the 3 groups. When subjected to stimulation with moderate to high flash intensities, eyes that had received intravitreal injections of triamcinolone (groups 1 and 3) had a 10% to 25% increase in dark-adapted a- and b-wave electroretinographic amplitudes. No histologic differences were observed between injected and control eyes. CONCLUSIONS: Intravitreal injection of 4 mg of triamcinolone acetonide does not cause a toxic reaction in the rabbit retina after 7 days. Triamcinolone therapy may augment the rod-driven electroretinographic responses, suggesting a mechanism by which visual function may improve. Clinical Relevance Evaluation of the toxic effects of triamcinolone is useful because of increased applications of intravitreal injection.

The challenge of preventing vision loss from diabetic retinopathy.

Diabetes is present in 7% of Missourians. Another 52% are at risk. Periodic eye examinations are key to averting vision loss from diabetic retinopathy. Signs of diabetic retinopathy are evident long before vision loss and include microaneurysms, retinal hemorrhage, microvascular and venous caliber abnormalities and neovascularization. Loss of vascular integrity can lead to retinal edema and neovascular growth. Laser ablation of the peripheral retina can curb neovascular growth. It can also help stabilize macular edema.

Effect of intensive diabetes therapy on the progression of diabetic retinopathy in patients with type 1 diabetes: 18 years of follow-up in the DCCT/EDIC.

The Diabetes Control and Complications Trial (DCCT) demonstrated that a mean of 6.5 years of intensive therapy aimed at near-normal glucose levels reduced the risk of development and progression of retinopathy by as much as 76% compared with conventional therapy. The Epidemiology of Diabetes Interventions and Complications study (EDIC) observational follow-up showed that the risk of further progression of retinopathy 4 years after the DCCT ended was also greatly reduced in the former intensive group, despite nearly equivalent levels of HbA1c, a phenomenon termed metabolic memory. Metabolic memory was shown to persist through 10 years of follow-up. We now describe the risk of further progression of retinopathy, progression to proliferative diabetic retinopathy, clinically significant macular edema, and the need for intervention (photocoagulation or anti-VEGF) over 18 years of follow-up in EDIC. The cumulative incidence of each retinal outcome continues to be lower in the former intensive group. However, the year-to-year incidence of these outcomes is now similar, owing in large part to a reduction in risk in the former conventional treatment group.