VISUAL OUTCOMES AFTER INTERNAL LIMITING MEMBRANE PEELING VERSUS FLAP IN THE CLOSURE OF FULL-THICKNESS MACULAR HOLES.

PURPOSE: To examine postoperative outcomes of internal limiting membrane peeling (ILMP) versus flap (ILMF) in the closure of full-thickness macular holes. METHODS: Retrospective chart review of patients who underwent pars plana vitrectomy and gas tamponade with ILMP or ILMF to close full-thickness macular hole at the Atrium Health Wake Forest Baptist from January 2012 to October 2022 with at least 3 months follow-up. Main outcome measures were type 1 primary full-thickness macular hole closure and postoperative best-corrected visual acuity in mean logMAR. RESULTS: One hundred thirty and 30 eyes underwent ILMP and ILMF, respectively. There were no significant differences in baseline characteristics between the groups. Ninety-six percent of ILMP eyes and 90% of ILMF eyes achieved primary hole closure ( P = 0.29). Among all eyes with primary hole closure, best-corrected visual acuity at 1 year was not different between the groups, but when stratified by lens status, it was superior in the ILMP versus ILMF group in pseudophakic eyes: the estimated least-squares mean best-corrected visual acuity (Snellen equivalent) (95% confidence interval) was 0.42 (20/50) (0.34, 0.49) in the ILMP group and 0.71 (20/100) (0.50, 0.92) in the ILMF group. CONCLUSION: Internal limiting membrane peeling and ILMF techniques yielded similarly high full-thickness macular hole closure rates. In pseudophakic eyes with primary hole closure, ILMF eyes had worse best-corrected visual acuity at 1 year.

The effects of medical management on the progression of diabetic retinopathy in persons with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study.

PURPOSE: To report additional ocular outcomes of intensive treatment of hyperglycemia, blood pressure, and dyslipidemia in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. DESIGN: Double 2×2 factorial, multicenter, randomized clinical trials in people with type 2 diabetes who had cardiovascular disease or cardiovascular risk factors. In the glycemia trial, targets of intensive and standard treatment were: hemoglobin A1c <6.0% and 7.0% to 7.9%, respectively, and in the blood pressure trial: systolic blood pressures of <120 and <140 mmHg, respectively. The dyslipidemia trial compared fenofibrate plus simvastatin with placebo plus simvastatin. PARTICIPANTS: Of the 3472 ACCORD Eye Study participants enrolled, 2856 had 4-year data (85% of survivors). METHODS: Eye examinations and fundus photographs were taken at baseline and year 4. Photographs were graded centrally for retinopathy severity and macular edema using the Early Treatment Diabetic Retinopathy Study (ETDRS) methods. MAIN OUTCOME MEASURES: Three or more steps of progression on the ETDRS person scale or treatment of retinopathy with photocoagulation or vitrectomy. RESULTS: As previously reported, there were significant reductions in the primary outcome in the glycemia and dyslipidemia trials, but no significant effect in the blood pressure trial. Results were similar for retinopathy progression by 1, 2, and 4 or more steps on the person scale and for ≥ 2 steps on the eye scale. In the subgroup of patients with mild retinopathy at baseline, effect estimates were large (odds ratios, ∼0.30; P < 0.001), but did not reach nominal significance for participants with no retinopathy or for those with moderate to severe retinopathy at baseline. CONCLUSIONS: Slowing of progression of retinopathy by intensive treatment of glycemia was observed in ACCORD participants, whose average age and diabetes duration were 62 and 10 years, respectively, and who had cardiovascular disease or cardiovascular risk factors. The effect seemed stronger in patients with mild retinopathy. Similar slowing of progression was observed in patients treated with fenofibrate, with no effect observed with intensive blood pressure treatment. This is the second study to confirm the benefits of fenofibrate in reducing diabetic retinopathy progression, and fenofibrate should be considered for treatment of diabetic retinopathy.

Effects of medical therapies on retinopathy progression in type 2 diabetes.

BACKGROUND: We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type 2 diabetes. Previous data suggest that these systemic factors may be important in the development and progression of diabetic retinopathy. METHODS: In a randomized trial, we enrolled 10,251 participants with type 2 diabetes who were at high risk for cardiovascular disease to receive either intensive or standard treatment for glycemia (target glycated hemoglobin level, <6.0% or 7.0 to 7.9%, respectively) and also for dyslipidemia (160 mg daily of fenofibrate plus simvastatin or placebo plus simvastatin) or for systolic blood-pressure control (target, <120 or <140 mm Hg). A subgroup of 2856 participants was evaluated for the effects of these interventions at 4 years on the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study Severity Scale (as assessed from seven-field stereoscopic fundus photographs, with 17 possible steps and a higher number of steps indicating greater severity) or the development of diabetic retinopathy necessitating laser photocoagulation or vitrectomy. RESULTS: At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval [CI], 0.51 to 0.87; P=0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P=0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio, 1.23; 95% CI, 0.84 to 1.79; P=0.29). CONCLUSIONS: Intensive glycemic control and intensive combination treatment of dyslipidemia, but not intensive blood-pressure control, reduced the rate of progression of diabetic retinopathy. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov numbers, NCT00000620 for the ACCORD study and NCT00542178 for the ACCORD Eye study.)

Green or yellow laser treatment for diabetic macular edema: exploratory assessment within the Diabetic Retinopathy Clinical Research Network.

PURPOSE: Explore differences in green compared with yellow focal/grid laser treatment on functional and anatomical endpoints in eyes with diabetic macular edema. METHODS: Data from two randomized clinical trials were evaluated for differences in visual acuity and optical coherence tomography parameters for eyes assigned to sham injection + prompt laser, ranibizumab + prompt laser, or prompt laser only: among subgroups of eyes treated exclusively and electively with either green or yellow laser. RESULTS: In the sham injection + prompt laser group, the mean visual acuity letter score change for eyes receiving green and yellow laser treatment, respectively, was +2.4 ± 14 and +5.1 ± 13 at the 52-week visit (P = 0.06) and +2.4 ± 15 and +6.0 ± 13 at the 104-week visit (P = 0.13), with no corresponding evidence of differences in optical coherence tomography thickness. When comparing wavelength groups in the ranibizumab + prompt laser and prompt laser-only groups, meaningful differences in visual acuity and optical coherence tomography thickness were not detected at 1 year or 2 years. CONCLUSION: A trend toward improved vision outcome with yellow laser observed in one trial was not corroborated by anatomical outcomes or by the other trial. In this study, without random assignment to different wavelengths controlling for bias and confounding, it is not possible to determine whether one wavelength is better than the other.

Comparison of standardized clinical classification with fundus photograph grading for the assessment of diabetic retinopathy and diabetic macular edema severity.

PURPOSE: To compare evaluation by clinical examination with image grading at a reading center for the classification of diabetic retinopathy and diabetic macular edema. METHODS: Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Family Investigations of Nephropathy in Diabetes (FIND) had similar methods of clinical and fundus photograph evaluation. For analysis purposes, the photographic grading scales were condensed to correspond to the clinical scales, and agreement between clinicians and reading center classification were compared. RESULTS: Six thousand nine hundred and two eyes of ACCORD participants and 3,638 eyes of FIND participants were analyzed for agreement (percent, kappa) on diabetic retinopathy on a 5-level scale. Exact agreement between clinicians and reading center on diabetic retinopathy severity category was 69% in ACCORD and 74% in FIND (kappa 0.42 and 0.65). Sensitivities of the clinical grading to identify the presence of mild nonproliferative retinopathy or worse were 0.53 in ACCORD and 0.84 in FIND. Specificities were 0.97 and 0.96, respectively. Diabetic macular edema agreement in 6,649 eyes of ACCORD participants and 3,366 eyes of FIND participants was similar (kappa 0.35 and 0.41). Sensitivities of the clinical grading to identify diabetic macular edema were 0.44 and 0.53 and specificities were 0.99 and 0.94, respectively. CONCLUSION: The results support the use of clinical information for defining broad severity categories but not for documenting small-to-moderate changes in diabetic retinopathy over time.

REPAIR OF COMBINED TRACTION-RHEGMATOGENOUS RETINAL DETACHMENT AFTER CRYOABLATION OF A RETINAL CAPILLARY HEMANGIOBLASTOMA.

PURPOSE: To describe a case of surgical repair of a total, combined traction-rhegmatogenous, retinal detachment with proliferative vitreoretinopathy after cryoablation of a retinal capillary hemangioblastoma. METHODS: A case of a 47-year-old man presenting with a solitary, superotemporal retinal capillary hemangioblastoma in the right eye with serous retinal detachment and subfoveal fluid and exudates is reported. The hemangioblastoma was treated with cryoablation, but despite regression of the lesion, the patient developed a total combined traction-rhegmatogenous retinal detachment 6 weeks later. Vitrectomy, endolaser photocoagulation to tears adjacent to the original hemangioblastoma lesion, and silicone oil exchange was performed to repair the detachment. RESULTS: Eighteen months after initial repair, the patient had silicone oil removal and cataract extraction with lens implantation. Final visual acuity improved from counting fingers to 20/50 with total retinal reattachment and regression of the retinal capillary hemangioblastoma. CONCLUSION: Although uncommon, combined traction-rhegmatogenous retinal detachment can occur after cryoablation of a retinal capillary hemangioblastoma.

Visual Acuity Outcomes in Diabetic Macular Edema With Fluocinolone Acetonide 0.2 µg/Day Versus Ranibizumab Plus Deferred Laser (DRCR Protocol I).

BACKGROUND AND OBJECTIVE: Visual outcomes of the FAME study (0.2 µg/day fluocinolone acetonide [FAc]) and Protocol I (0.5 mg ranibizumab plus deferred laser) were compared using the area under the curve (AUC) analysis method. PATIENTS AND METHODS: Best-corrected visual acuity (BCVA) data collected during a period of 3 years of follow-up for patients enrolled in FAME or Protocol I were used to calculate AUC of the change in BCVA over a time curve. RESULTS: In the overall population, there was a greater treatment effect for ranibizumab plus deferred laser compared with FAc. However, for subgroups of pseudophakic eyes, eyes with chronic diabetic macular edema (DME), and pseudophakic eyes with chronic DME, ranibizumab plus deferred laser and FAc were not found to be significantly different. The ranibizumab group received a median of 14 injections during a 36-month period compared with a mean of 1.3 injections in the FAc group. CONCLUSION: In pseudophakic and chronic DME subgroups, FAc was comparable to ranibizumab plus deferred laser with fewer injections. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:698-706.].

Lack of Longitudinal Association Between Thiazolidinediones and Incidence and Progression of Diabetic Eye Disease: The ACCORD Eye Study.

PURPOSE: To report the longitudinal association between use of thiazolidinediones (TZDs), visual acuity (VA) change, and diabetic eye disease incidence and progression. DESIGN: Cohort study ancillary to a randomized clinical trial. METHODS: We analyzed baseline and 4-year follow-up data of 2856 ACCORD trial participants with no history of proliferative diabetic retinopathy. Based on stereoscopic fundus photographs, we evaluated diabetic macular edema (DME) progression and DR progression. We also evaluated 10- and 15-letter change on the ETDRS visual acuity chart. Main outcome measures were incidence or progression of DME or DR and change in visual acuity. RESULTS: TZD use was not associated with DME incidence in either the analysis of any use (adjusted odds ratio [aOR] [95% CI]: 1.22 [0.72-2.05]) or duration of use (aOR: 1.02 [0.99-1.04]). Diabetic retinopathy (DR) incidence/progression was more common in patients with no or mild DR at baseline who were ever treated with TZDs (aOR: 1.68 [1.11-2.55]), but this association disappeared when adjusting for the time on TZD (aOR: 1.02 [1.00-1.04]). DR progression among those with moderate or worse DR at baseline was no different between TZD users and non-users. TZD usage had no effect on the ultimate visual acuity outcome. CONCLUSION: In this longitudinal study of patients with type 2 diabetes, we found no association between TZD use and visual acuity outcomes or DME progression, and no consistent evidence of increased DR progression in patients ever treated with TZDs vs those never treated with TZDs.

Rationale, design, and methods of the Action to Control Cardiovascular Risk in Diabetes Eye Study (ACCORD-EYE).

Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus. The Action to Control Cardiovascular Risk in Diabetes Eye Study (ACCORD-EYE), a prospective study of a subset of patients in the randomized controlled clinical ACCORD trial, is being conducted at enrollment and after 4 years of follow-up to assess the progression of DR with standardized comprehensive eye exams and fundus photography of 7 standard stereoscopic fields. This study aims to assess the effects of the ACCORD medical treatment strategies of tight control of glycemia and blood pressure and management of dyslipidemia on the course of DR in patients with type 2 diabetes. Photographs will be evaluated at a centralized location using the modified Early Treatment Diabetic Retinopathy Study (ETDRS) classification. The primary outcome of ACCORD-EYE, which will measure the development and progression of DR, is a composite of (1) progression of DR (> or = 3 steps on the ETDRS scale), (2) photocoagulation for DR, or (3) vitrectomy for DR. Specifically, the following questions will be addressed: (1) Does a therapeutic strategy targeting a glycosylated hemoglobin (HbA(1c)) level <6.0% reduce development and progression of DR more than one targeting an HbA(1c) level of 7.0%-7.9% (target median level, 7.5%)? (2) In the context of good glycemic control, does a strategy using a fibrate to increase high-density lipoprotein cholesterol and lower triglyceride levels and a statin to maintain the level of low-density lipoprotein (LDL) cholesterol at <2.59 mmol/L (100 mg/dL) reduce development and progression of DR compared with one using placebo and a statin to treat LDL cholesterol? (3) In the context of good glycemic control, does a strategy targeting a systolic blood pressure level <120 mm Hg reduce development and progression of DR compared with one targeting a level <140 mm Hg? Secondary outcome variables include various levels of loss of visual acuity at 4 years versus baseline, cataract extraction, and the development or progression of diabetic macular edema. Methods to measure DR progression have been incorporated into ACCORD, and complete baseline data have been collected on 3,537 participants. These data will provide valuable information regarding the effects of medical treatment on the prevention and progression of DR.

A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema.

OBJECTIVE: To provide data on the short-term effect of intravitreal bevacizumab for diabetic macular edema (DME). DESIGN: Randomized phase II clinical trial. PARTICIPANTS: One hundred twenty-one eyes of 121 subjects (109 eligible for analysis) with DME and Snellen acuity equivalent ranging from 20/32 to 20/320. INTERVENTIONS: Random assignment to 1 of 5 groups: (A) focal photocoagulation at baseline (n = 19), (B) intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks (n = 22), (C) intravitreal injection of 2.5 mg of bevacizumab at baseline and 6 weeks (n = 24), (D) intravitreal injection of 1.25 mg of bevacizumab at baseline and sham injection at 6 weeks (n = 22), or (E) intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks with photocoagulation at 3 weeks (n = 22). MAIN OUTCOME MEASURES: Central subfield thickness (CST) on optical coherence tomography and best-corrected visual acuity (VA) were measured at baseline and after 3, 6, 9, 12, 18, and 24 weeks. RESULTS: At baseline, median CST was 411 mum and median Snellen VA equivalent was 20/50. Compared with group A, groups B and C had a greater reduction in CST at 3 weeks and about 1 line better median VA over 12 weeks. There were no meaningful differences between groups B and C in CST reduction or VA improvement. A CST reduction > 11% (reliability limit) was present at 3 weeks in 36 of 84 (43%) bevacizumab-treated eyes and 5 of 18 (28%) eyes treated with laser alone, and at 6 weeks in 31 of 84 (37%) and 9 of 18 (50%) eyes, respectively. Combining focal photocoagulation with bevacizumab resulted in no apparent short-term benefit or adverse outcomes. Endophthalmitis developed in 1 eye. The following events occurred during the first 24 weeks in subjects treated with bevacizumab without attributing cause to the drug: myocardial infarction (n = 2), congestive heart failure (n = 1), elevated blood pressure (n = 3), and worsened renal function (n = 3). CONCLUSION: These results demonstrate that intravitreal bevacizumab can reduce DME in some eyes, but the study was not designed to determine whether treatment is beneficial. A phase III trial would be needed for that purpose.

Choroidal Melanoma Mimicker: A Case of Metastatic Clear-Cell Renal Cell Carcinoma.

Choroidal melanoma is the most common primary intraocular malignancy, yet metastatic disease remains the most common malignancy of the eye. Differentiating these entities is essential as treatment, systemic associations, and prognosis vary dramatically between the two. Established diagnostic criteria are accurate for the diagnosis of uveal melanoma. Yet, metastatic disease may be misdiagnosed as a uveal melanoma in rare cases. We report a case of metastatic clear-cell renal cell carcinoma masquerading as uveal melanoma. A 73-year-old Caucasian man with a history of renal cell carcinoma presented with a 15 × 12 × 7 mm homogenous, pigmented, and acoustically hollow mass without hemorrhage or exudation. The patient was initially treated with plaque radiotherapy with good tumor regression. However, the patient developed pain and vision loss due to total exudative retinal detachment. Subsequent enucleation allowed histopathologic confirmation of clear-cell renal cell carcinoma. Nine years following enucleation, the patient remains in complete remission without evidence of other systemic metastases. Renal cell carcinoma should be considered when evaluating patients with probable uveal melanoma. Delayed-onset ocular metastasis from renal cell carcinoma exhibits an atypical clinical course with the possibility of durable remission following enucleation.

Circumstance and outcome of ocular paintball injuries.

PURPOSE: To determine the circumstance and outcome of ocular injuries attributable to paintball projectiles. DESIGN: Retrospective interventional case series. METHODS: Institutional review board approved retrospective chart review of 19 consecutive eyes with paintball injuries with minimum follow-up of 3 months. RESULTS: Ten eyes (53%) had final visual acuity of 20/40 or better, while seven (36%) were 20/200 or worse. Ten eyes were injured in paintball games, (two formal and eight informal), while nine (47%) were injured by accidents or assaults not associated with any "game." CONCLUSIONS: Paintball injuries often cause severe and permanent visual loss. Nearly half of these injuries occur outside a war game setting as accidents or assaults.

Application of random forests methods to diabetic retinopathy classification analyses.

BACKGROUND: Diabetic retinopathy (DR) is one of the leading causes of blindness in the United States and world-wide. DR is a silent disease that may go unnoticed until it is too late for effective treatment. Therefore, early detection could improve the chances of therapeutic interventions that would alleviate its effects. METHODOLOGY: Graded fundus photography and systemic data from 3443 ACCORD-Eye Study participants were used to estimate Random Forest (RF) and logistic regression classifiers. We studied the impact of sample size on classifier performance and the possibility of using RF generated class conditional probabilities as metrics describing DR risk. RF measures of variable importance are used to detect factors that affect classification performance. PRINCIPAL FINDINGS: Both types of data were informative when discriminating participants with or without DR. RF based models produced much higher classification accuracy than those based on logistic regression. Combining both types of data did not increase accuracy but did increase statistical discrimination of healthy participants who subsequently did or did not have DR events during four years of follow-up. RF variable importance criteria revealed that microaneurysms counts in both eyes seemed to play the most important role in discrimination among the graded fundus variables, while the number of medicines and diabetes duration were the most relevant among the systemic variables. CONCLUSIONS AND SIGNIFICANCE: We have introduced RF methods to DR classification analyses based on fundus photography data. In addition, we propose an approach to DR risk assessment based on metrics derived from graded fundus photography and systemic data. Our results suggest that RF methods could be a valuable tool to diagnose DR diagnosis and evaluate its progression.

The degree of retinopathy is equally predictive for renal and macrovascular outcomes in the ACCORD Trial.

AIMS: Diabetic retinopathy (DR) is associated with a higher risk of renal and cardiovascular events. We sought to compare the risk for renal versus cardiovascular (CV) outcomes, stratified by retinopathy severity. METHODS: ACCORD was a randomized trial of people with type 2 diabetes, at high-risk for CV disease. A subgroup (n=3,369 from 71 clinics) had stereoscopic fundus photographs graded centrally. Participants were stratified at baseline to moderate/severe DR or no/mild DR and were monitored for renal and CV outcomes at follow-up visits over 4 years. The composite renal outcome was composed of serum creatinine doubling, macroalbuminuria, or end-stage renal disease. The composite CV outcome was the ACCORD trial primary outcome. Competing risk techniques were used to estimate the relative risk (RR) of renal versus CV composite outcomes within each DR stratum. RESULTS: The hazards ratio for doubling of serum creatinine and incident CV event in the moderate/severe DR versus no/mild DR strata were: 2.31 (95% CI: 1.25-4.26) and 1.98 (95% CI: 1.49-2.62), respectively. The RR of the two composite outcomes was highly similar in the no/mild DR stratum (adjusted RR at 4 years for CV versus renal events=0.96, 95% CI: 0.72-1.28) and the moderate/severe DR stratum (adjusted RR=0.92, 95% CI: 0.64-1.31). CONCLUSIONS: Thus, in people with type 2 diabetes at high risk for cardiovascular disease, incident CV versus renal events was similar, irrespective of the severity of the DR. Further evaluation of the specificity of DR for microvascular versus macrovascular events in other populations is warranted.

Bilateral Candida endophthalmitis in a premature infant.

Endogenous infantile Candida endophthalmitis is a rare but potentially devastating condition resulting from sequestration of the fungus within the lens after systemic infection. We report the case of a 20-week-old girl with a history of Candida sepsis who presented with bilateral Candida albicans endophthalmitis 15 weeks after completing a 6-week course of intravenous antifungal therapy. Prompt vitrectomy resulted in salvage of the right eye, although a total retinal detachment occurred. Cataract extraction and administration of intravenous and intravitreal amphotericin B preserved vision in the left eye.

Intravitreal moxifloxacin in the management of Ochrobactrum intermedium endophthalmitis due to metallic intraocular foreign body.

A healthy 34-year-old man presented with Ochrobactrum intermedium endophthalmitis due to a metallic intraocular foreign body. After vitrectomy, lensectomy, removal of the metallic intraocular foreign body, intravitreal vancomycin and ceftazidime, and systemic ciprofloxacin, intraocular inflammation worsened. Repeat vitreous culture confirmed persistent endophthalmitis due to multidrug-resistant O. intermedium. The endophthalmitis successfully resolved after the administration of intravitreal moxifloxacin.