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.

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.

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.

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.

Alternative dose for choroidal melanoma treated with an iodine-125 radioactive plaque: a single-institution retrospective study.

PURPOSE: The Collaborative Ocular Melanoma Study (COMS) established iodine-125 plaque brachytherapy as an accepted standard treatment for medium-size choroidal melanoma. In the COMS, the prescription dose was 85 Gy. This is a retrospective review of our outcomes in patients treated with lower doses than those used in the COMS. METHODS AND MATERIALS: From 1990 to 2004, 62 patients were treated with iodine-125 plaque brachytherapy for choroidal melanoma. COMS eye plaques were used with dose prescribed to the apex of the tumor. The median and average dose rates at the tumor apex were 63.5 cGy/h and 62.7 cGy/h, respectively. The median and average total doses were 63.0 Gy and 62.5 Gy (range, 56-69 Gy), respectively. The median and mean durations of implant were 100.0 hours and 101.1 hours (range, 71-165 hours). RESULTS: Median follow-up time was 58.2 months. The 5-year outcomes including overall survival, disease-free survival, cause-specific survival, local failure, secondary enucleation rate, and visual acuity (VA) <20/200 were estimated using the Kaplan-Meier method. Overall, there were 7 local failures, 4 distant failures, and 10 secondary enucleations (6 due to local failure and 4 due to treatment complications). Univariate analysis was performed to identify significant prognostic factors associated with disease-free survival (baseline VA in tumor eye, tumor shape), cause-specific survival (diabetic retinopathy), local failure (none found), secondary enucleation rate (diabetic retinopathy, basal tumor dimension) and VA <20/200 (diabetic retinopathy, tumor shape, age, retinal detachment, treatment depth, and history of vision-limiting condition). CONCLUSIONS: Our survival and local control outcomes are comparable to those of the COMS. However, VA at 5 years seems to be better. Lower doses of radiation could potentially lead to better visual outcomes.

Lack of association between thiazolidinediones and macular edema in type 2 diabetes: the ACCORD eye substudy.

OBJECTIVE: To assess the cross-sectional association of thiazolidinediones with diabetic macular edema (DME). METHODS: The cross-sectional association of DME and visual acuity with thiazolidinediones was examined by means of baseline fundus photographs and visual acuity measurements from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Visual acuity was assessed in 9690 participants in the ACCORD trial, and 3473 of these participants had fundus photographs that were centrally read in a standardized fashion by masked graders to assess DME and retinopathy from October 23, 2003, to March 10, 2006. RESULTS: Among the subsample, 695 (20.0%) people had used thiazolidinediones, whereas 217 (6.2%) people had DME. Thiazolidinedione use was not associated with DME in unadjusted (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.71-1.44; P = .95) and adjusted (OR, 0.97; 95% CI, 0.67-1.40; P = .86) analyses. Significant associations with DME were found for retinopathy severity (P < .001) and age (OR, 0.97; 95% CI, 0.952-0.997; P = .03) but not for hemoglobin A(1c) (P = .06), duration of diabetes (P = .65), sex (P = .72), and ethnicity (P = .20). Thiazolidinedione use was associated with slightly greater visual acuity (0.79 letter; 95% CI, 0.20-1.38; P = .009) of uncertain clinical significance. CONCLUSIONS: In a cross-sectional analysis of data from the largest study to date, no association was observed between thiazolidinedione exposure and DME in patients with type 2 diabetes; however, we cannot exclude a modest protective or harmful association. Trial Registration clinicaltrials.gov Identifier: NCT00542178.

Avoiding and managing the dislocated crystalline lens.

A major complication of cataract surgery is the posterior dislocation of crystalline lens material, which may lead to poor visual outcomes. Knowledge of preoperative high-risk situations, causes of lens dislocation, and intraoperative warning signs should lead to reduced complications. This update reviews techniques to avoid the dislocated lens, and management options if this complication does occur.

Delayed visual loss after pars plana vitrectomy for retained lens fragments.

PURPOSE: To report visual results and postoperative complications in patients undergoing vitrectomy for retained lens fragments. METHODS: Retrospective, noncomparative, interventional case series of 42 consecutive patients undergoing vitrectomy for retained lens fragments by a single surgeon, all with a minimum of 6 months' follow-up. The main outcome measurement was best corrected visual acuity at 3 months and at final follow-up visit. RESULTS: Although 67% of eyes achieved a postoperative visual acuity of 20/40 or better at 3 months, 17% had events during follow-up that resulted in loss of vision to less than 20/40. Final best corrected visual acuity 20/40 or better was achieved in 50% of eyes. Retinal detachment occurred in 17%, and 21% of eyes required long-term therapy for glaucoma. CONCLUSION: Patients undergoing vitrectomy for retained lens fragments often develop delayed visual loss. Long-term surveillance is necessary in these patients.

Visual results, prognostic indicators, and posterior segment findings following surgery for cataract/lens subluxation-dislocation secondary to ocular contusion injuries.

OBJECTIVE: To determine visual outcomes, incidence of posterior segment abnormalities, and prognostic factors in eyes undergoing lens removal for cataract or lens subluxation-dislocation secondary to ocular contusion injuries. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Forty eyes in forty consecutive patients undergoing lens extraction for ocular contusion-related cataract or lens subluxation, all with a minimum of 6 months' follow-up. INTERVENTION: Lens extraction in the traumatized eye. MAIN OUTCOME MEASURE: Final best-corrected visual acuity. RESULTS: Final best-corrected visual acuity was 20/40 or better in 55% of eyes, and ambulatory vision (>5/200) was achieved in 88%. Preoperative factors associated with poorer visual outcome (<20/40) were the presence of an afferent pupillary defect or an iridodialysis (P < 0.05). Seventy percent of eyes were determined to have significant posterior segment injuries. The cause of final visual acuity less than 20/40 included macular scarring (23%), retinal detachment (15%), and optic atrophy (5%). CONCLUSION: Cataract or lens subluxation secondary to ocular contusion injuries is often associated with severe posterior segment sequelae and poor visual outcomes.