Jeffrey G. Gross

Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial

IMPORTANCE Panretinal photocoagulation (PRP) is the standard treatment for reducing severe visual loss from proliferative diabetic retinopathy. However, PRP can damage the retina, resulting in peripheral vision loss or worsening diabetic macular edema (DME). OBJECTIVE To evaluate the noninferiority of intravitreous ranibizumab compared with PRP for visual acuity outcomes in patients with proliferative diabetic retinopathy. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 (mean age, 52 years; 44% female; 52% white). Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015. INTERVENTIONS Individual eyes were randomly assigned to receive PRP treatment, completed in 1 to 3 visits (n = 203 eyes), or ranibizumab, 0.5 mg, by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol (n = 191 eyes). Eyes in both treatment groups could receive ranibizumab for DME. MAIN OUTCOMES AND MEASURES The primary outcome was mean visual acuity change at 2 years (5-letter noninferiority margin; intention-to-treat analysis). Secondary outcomes included visual acuity area under the curve, peripheral visual field loss, vitrectomy, DME development, and retinal neovascularization. RESULTS Mean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group vs +0.2 in the PRP group (difference, +2.2; 95% CI, -0.5 to +5.0; P < .001 for noninferiority). The mean treatment group difference in visual acuity area under the curve over 2 years was +4.2 (95% CI, +3.0 to +5.4; P < .001). Mean peripheral visual field sensitivity loss was worse (-23 dB vs -422 dB; difference, 372 dB; 95% CI, 213-531 dB; P < .001), vitrectomy was more frequent (15% vs 4%; difference, 9%; 95% CI, 4%-15%; P < .001), and DME development was more frequent (28% vs 9%; difference, 19%; 95% CI, 10%-28%; P < .001) in the PRP group vs the ranibizumab group, respectively. Eyes without active or regressed neovascularization at 2 years were not significantly different (35% in the ranibizumab group vs 30% in the PRP group; difference, 3%; 95% CI, -7% to 12%; P = .58). One eye in the ranibizumab group developed endophthalmitis. No significant differences between groups in rates of major cardiovascular events were identified. CONCLUSIONS AND RELEVANCE Among eyes with proliferative diabetic retinopathy, treatment with ranibizumab resulted in visual acuity that was noninferior to (not worse than) PRP treatment at 2 years. Although longer-term follow-up is needed, ranibizumab may be a reasonable treatment alternative, at least through 2 years, for patients with proliferative diabetic retinopathy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01489189.

Retinal Thickness on Stratus Optical Coherence Tomography in People with Diabetes and Minimal or No Diabetic Retinopathy

PURPOSE To evaluate optical coherence tomography (OCT) thickness of the macula in people with diabetes but minimal or no retinopathy and to compare these findings with published normative data in the literature from subjects reported to have no retinal disease. DESIGN Cross-sectional study. METHODS In a multicenter community- and university-based practices setting, 97 subjects with diabetes with no or minimal diabetic retinopathy and no central retinal thickening on clinical examination and a center point thickness of 225 microm or less on OCT (Stratus OCT; Carl Zeiss Meditec, Dublin, California, USA) were recruited. Electronic Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity, seven-field stereoscopic color fundus photographs, and Stratus OCT fast macular scan were noted. Main outcome measures were central subfield (CSF) thickness measured on Stratus OCT. RESULTS On average, CSF thickness was 201 +/- 22 microm. CSF thickness was significantly greater in retinas from men than retinas from women (mean +/- standard deviation, 209 +/- 18 microm vs 194 +/- 23 microm; P < .001). After adjusting for gender, no additional factors were found to be associated significantly with CSF thickness (P > .10). CONCLUSIONS CSF thicknesses on Stratus OCT in people with diabetes and minimal or no retinopathy are similar to thicknesses reported from a normative database of people without diabetes. CSF thickness is greater in men than in women, consistent with many, but not all, previous reports. Studies involving comparisons of retinal thickness with expected norms should consider different mean values for women and men.

Observational study of the development of diabetic macular edema following panretinal (scatter) photocoagulation given in 1 or 4 sittings.

OBJECTIVE To compare the effects of single-sitting vs 4-sitting panretinal photocoagulation (PRP) on macular edema in subjects with severe nonproliferative or early proliferative diabetic retinopathy with relatively good visual acuity and no or mild center-involved macular edema. METHODS Subjects were treated with 1 sitting or 4 sittings of PRP in a nonrandomized, prospective, multicentered clinical trial. Main Outcome Measure Central subfield thickness on optical coherence tomography (OCT). RESULTS Central subfield thickness was slightly greater in the 1-sitting group (n = 84) than in the 4-sitting group (n = 71) at the 3-day (P = .01) and 4-week visits (P = .003). At the 34-week primary outcome visit, the slight differences had reversed, with the thickness being slightly greater in the 4-sitting group than in the 1-sitting group (P = .06). Visual acuity differences paralleled OCT differences. CONCLUSIONS Our results suggest that clinically meaningful differences are unlikely in OCT thickness or visual acuity following application of PRP in 1 sitting compared with 4 sittings in subjects in this cohort. More definitive results would require a large randomized trial. Application to Clinical Practice These results suggest PRP costs to some patients in terms of travel and lost productivity as well as to eye care providers could be reduced. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00687154.

Subfoveal Neovascular Membrane Removal in Patients with Traumatic Choroidal Rupture

PURPOSE To describe the clinical outcomes of patients undergoing pars plana vitrectomy to remove subretinal neovascular membranes caused by traumatic choroidal ruptures. METHODS Three patients with traumatic choroidal rupture in whom subfoveal choroidal neovascularization developed underwent pars plana vitrectomy with surgical excision of the neovascular membrane. Surgical specimens were examined histopathologically in two patients. RESULTS The choroidal neovascularization was removed completely in each patient. Visual results were excellent with visual acuities improving to 20/30 or better in each patient. Recurrence of choroidal neovascularization has not been observed. Fibrovascular membranes with reactive retinal pigment epithelium were observed in two specimens examined histopathologically. CONCLUSION Surgical removal of subretinal neovascular membranes emanating from traumatic choroidal ruptures produced an excellent visual outcome in three patients studied. The neovascular membranes, which were removed with minor disturbance to the underlying pigment epithelium, have similar characteristics to those obtained from patients with ocular histoplasmosis syndrome.

Pathologic observations made by retinal biopsy.

The authors report four cases in which retinal biopsy findings yielded unexpected or previously unreported diagnoses in patients with inflammatory retinitis. The tissue diagnoses included Wegeners retinal vasculitis in an immunosuppressed patient with a clinical diagnosis of cytomegalovirus retinitis, a novel viral form in the retina of a patient with cytomegalovirus retinitis, a case of acute retinal necrosis due to cytomegalovirus infection in an immunologically normal adult, and a case of ganciclovir-resistant herpes family viral retinitis. These cases illustrate the use of retinal biopsy in obtaining tissue for diagnosis and guiding treatment in selected cases of retinitis.

ENDOGENOUS ASPERGILLUS-INDUCED ENDOPHTHALMITIS: Successful Treatment Without Systemic Antifungal Medication

A 32-year-old man had unilateral visual loss, a gravitational layering of preretinal inflammatory cells in the macula (pseudohypopyon), subretinal infiltrates, and hemorrhagic vasculitis. The patient initially denied intravenous drug abuse. Aspergillus terreus was cultured from undiluted vitreous obtained from a diagnostic and therapeutic vitrectomy specimen. Intravitreal and subconjunctival injections of amphotericin B alone were successful treatment. To the authors knowledge, antemortem diagnosis and treatment of A. terreus-induced endophthalmitis has not been reported previously. This article describes the second case of aspergillar endophthalmitis successfully treated without adjunctive systemic antifungal therapy.

Useful adjuncts for vitreoretinal surgery

Many vitreoretinal procedures are performed in offices and hospitals where cost control is important. We describe three useful devices and techniques that facilitate these procedures at minimal expense and often greater convenience. These include an accurate method for localising the pars plana without the use of callipers, an inexpensive, reliable, pressure regulated air pump for fluid-air exchange, and an easy method for intraocular injection of silicone oil through 20 gauge instrumentation without the need for expensive pumps. These procedures and techniques should prove to be useful in the treatment of vitreoretinal disease.

Magnetic Resonance Imaging in the Evaluation of Vitreoretinal Disease in Eyes with Intraocular Silicone Oil

Media opacification in eyes filled with silicone oil makes the evaluation of recurrent retinal detachment difficult. Ultrasonography through silicone oil is subject to significant imaging artifacts. We performed magnetic resonance imaging on six patients with unilateral intravitreal silicone oil to determine if the technique would detect detached retina and subretinal oil. All patients had undergone pars plana vitrectomy with silicone oil injection for proliferative vitreoretinopathy; five patients had encircling solid silicone scleral buckles. In five patients the media were clear, and ophthalmoscopic findings were correlated with magnetic resonance findings. Four patients had recurrence of inferior retinal detachment; magnetic resonance imaging demonstrated subretinal oil in three of these patients. One patient had a concentric, shallow, anterior retinal detachment; magnetic resonance scanning demonstrated a globular hyperintensity suggestive of subretinal oil. In the sixth patient, who had an opaque cornea, magnetic resonance imaging suggested that the retina was attached preoperatively; this was confirmed at subsequent surgery. A chemical shift artifact was helpful in defining the contour of retinal detachments and the presence of subretinal oil by outlining the silicone oil within the eye.

Posttraumatic yellow maculopathy.

Blunt trauma to the eye may cause several types of macular abnormalities, including commotio retinae, macular hole, intraretinal and subretinal hemorrhage, and choroidal rupture. In most cases the diagnosis is readily apparent; however, the complex appearance of simultaneous hemorrhage, pigmentary change, and ruptured tissue planes may be confusing. The authors present two cases of blunt trauma in young males that resulted in a subretinal hemorrhage that became yellow and was initially misinterpreted as a vitelliform lesion. A history of trauma should be sought in any patient with the clinical appearance of a yellow subretinal lesion.

Combined penetrating keratoplasty and vitreoretinal surgery with the Eckardt temporary keratoprosthesis

The Eckardt style temporary keratoprosthesis was used in six cases of five eyes undergoing simultaneous penetrating keratoplasty and pars plana vitrectomy. This device provided excellent visualization of posterior and peripheral intraocular structures and maintained a closed system during surgery. Corneal grafts remained clear in 80% of the cases, and macular attachment was achieved with either silicone oil or perfluoropropane gas in 50% of cases followed for at least 6 months. Visual function remained the same or improved in three eyes. Suggested refinements to the placement of this device include enlarging the trephination to 6.75 mm and the use of 8-0 nylon sutures to prevent cheesewiring of the soft silicone rim. A plano contact lens required during surgery to visualize the retina did not minify the image. Since the optical cylinder of the Eckardt temporary keratoprosthesis is shorter than that of a Landers-Foulks keratoprosthesis of similar diameter, it provides greater peripheral visualization. It is, however, less durable.