Timothy J. Murtha

Quantitative regional determination of morphometric indices of the total and perfused capillary network in the rat brain.

A new method has been developed to simultaneously and regionally determine various morphometric indices of the perfused and total capillary network in rat brain on a quantitative basis. A high molecular weight dextran, labeled with fluorescein isothiocyanate (FITC), was injected into the femoral vein of a barbiturate anesthetized rat. After 20 seconds, the animal was decapitated and the head frozen in liquid nitrogen. The anterior cortex, hypothalamus, thalamus, lenticulate nuclei, substantia nigra, hippocampus, posterior cortex, cerebellum, pons, and medulla were isolated and mounted in a microtome cryostat. Sections, 2 μm thick, were photographed with a fluorescent microscope to detect the perfused capillaries. The sections then were stained for alkaline phosphatase to visualize the total capillary network. Standard morphometric techniques were employed to determine the total and perfused volume, surface area, length, diameter, and number per mm3 from the photographs. The method was validated in brain, muscle, and omentum to show that the technique did not alter the capillary network, that both the total and perfused capillary network were visualized, and that there was little tissue shrinkage. The study found no significant differences in the total capillary network on a regional basis in rat brain in comparisons of any of the above indices in the 10 large brain areas. Similarly, it was found that the perfused capillary network was not different on a regional basis. Within the cortex, both total and perfused indices were greater in grey than white matter. The perfused capillary network ranged from 50.1% to 56.9% of total for the various indices determined. The percentage of the capillary network perfused increased significantly in a series of asphyxiated rats. Diameter of the capillaries in the control series averaged 6.05 ± 1.09 μm (mean ± SD) and was not significantly greater in the portion of the bed which was perfused.

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.

Macular edema after cataract surgery in eyes without preoperative central-involved diabetic macular edema.

IMPORTANCE The incidence of development or worsening of macular edema (ME) is variable in eyes without diabetic ME (DME) undergoing cataract surgery. OBJECTIVE To estimate the incidence of central-involved ME 16 weeks following cataract surgery in eyes with diabetic retinopathy without definite central-involved DME preoperatively. DESIGN, SETTING, AND PARTICIPANTS In a multicenter, prospective, observational study, 293 participants with diabetic retinopathy without definite central subfield thickening on optical coherence tomography (OCT) underwent cataract surgery. EXPOSURE Cataract extraction surgery performed within 28 days of enrollment of eyes without DME in individuals with diabetes mellitus. MAIN OUTCOMES AND MEASURES Development of central-involved ME defined as the following: (1) OCT central subfield thickness of 250 μm or greater (time-domain OCT) or 310 μm or greater (spectral-domain OCT) with at least a 1-step increase in logOCT central subfield thickness preoperatively to the 16-week visit; (2) at least a 2-step increase in logOCT central subfield thickness preoperatively to the 16-week visit; or (3) nontopical treatment for ME received before the 16-week visit with either of the OCT criteria met at the time of treatment. RESULTS The median participant age was 65 years. The median visual acuity letter score was 69 letters (Snellen equivalent 20/40). Forty-four percent of eyes had a history of treatment for DME. Sixteen weeks postoperatively, central-involved ME was noted in 0% (95% CI, 0%-20%) of 17 eyes with no preoperative DME. Of eyes with non-central-involved DME, 10% (95% CI, 5%-18%) of 97 eyes without central-involved DME and 12% (95% CI, 7%-19%) of 147 eyes with possible central-involved DME at baseline progressed to central-involved ME. History of DME treatment was significantly associated with central-involved ME development (P < .001). CONCLUSIONS AND RELEVANCE In eyes with diabetic retinopathy without concurrent central-involved DME, presence of non-central-involved DME immediately prior to cataract surgery or history of DME treatment may increase the risk of developing central-involved ME 16 weeks after cataract extraction.

The management of diabetic eye disease in the setting of cataract surgery.

Purpose of review The increased incidence of diabetes mellitus worldwide is accompanied by an increased risk of co-morbid conditions, including the intersection of diabetes, diabetic retinopathy and cataracts. In an effort to improve the surgical outcomes for this population, it is necessary to understand the historical perspectives that have evolved into current treatment recommendations. Recent findings While cataract surgery in patients with no or mild retinopathy may result in minimal complications, a substantial minority of patients with diabetes and advanced retinopathy, including macular edema and a history of previous laser treatment, may require additional considerations when planning cataract surgery. Untreated retinopathy, insufficiently treated retinopathy or treatment failures can be challenging. In these instances, a paradigm shift may be indicated, and the occasion of cataract surgery may provide an opportunity to simultaneously treat retinopathy. By utilizing combined vitrectomy/cataract surgical techniques and/or pharmacologic interventions, improved results for a broader diabetic population may be attainable. Summary Newer surgical and pharmacologic therapies may now allow for safe and effective surgery in individuals who were previously not candidates for surgery or who had a limited visual prognosis.

A RETROSPECTIVE ANALYSIS OF TRIPLE COMBINATION THERAPY WITH INTRAVITREAL BEVACIZUMAB, POSTERIOR SUB-TENONʼS TRIAMCINOLONE ACETONIDE, AND LOW-FLUENCE VERTEPORFIN PHOTODYNAMIC THERAPY IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION

Purpose: To assess the efficacy of triple combination therapy (TCT) including bevacizumab (BEV), low-fluence photodynamic therapy, and posterior sub-Tenons triamcinolone acetonide in patients with wet age-related macular degeneration. Methods: This institutional review board-approved retrospective consecutive case series included 31 eyes treated for wet age-related macular degeneration with TCT at the Beth Israel Deaconess Medical Center between June 2004 and November 2008. Outcome measures included visual acuity, retinal thickness as measured by optical coherence tomography, time to retreatment, and complications. Results: Triple combination therapy eyes showed significant 3-month and 6-month improvement in visual acuity of 0.140 ± 0.273 logarithm of the minimum angle of resolution and 0.182 ± 0.383 logarithm of the minimum angle of resolution after treatment, respectively (P = 0.0219 and 0.0470, respectively). Central retinal thickness significantly improved at 3 months (−123.8 ± 102.7 μm), 6 months (−87.7 ± 99.8 μm), and 12 months (−101.6 ± 103.3 μm) on optical coherence tomography. Half of eyes that underwent TCT required retreatment by the conclusion of their follow-up, and eyes that underwent TCT had a 1-year Kaplan-Meier survival rate of 62.1 ± 10.8%. Conclusion: Triple combination therapy (TCT) appears to effectively improve visual acuity and decrease retinal thickness often without need for subsequent retreatment within the first year of follow-up. Further investigation of TCT in prospective trials is warranted.

Automated Retinal Imaging System (ARIS) Compared with ETDRS Protocol Color Stereoscopic Retinal Photography to Assess Level of Diabetic Retinopathy

BACKGROUND Early Treatment Diabetic Retinopathy Study (ETDRS) seven-standard-field color stereoscopic retinal photography (ETDRS photos) has been a gold standard for determining diabetic retinopathy (DR) severity. The Automated Retinal Imaging System (ARIS™, model 110, Visual Pathways, Inc., Prescott, AZ) acquires seven-sequential color stereoscopic digital images (ARIS images) by a semiautomated technician-run process generally corresponding to ETDRS photos. We assessed the correlation between a single semiautomated ARIS imaging session without any re-imaging and ETDRS photos performed by a certified photographer for the determination of DR severity. METHODS Two independent masked readers graded mydriatic ARIS images and ETDRS photos. A third masked retinal specialist adjudicated discrepancies. Correlation between the two modalities was compared using weighted-κ statistics. RESULTS We evaluated 211 eyes of 106 patients with varying levels of DR. Partially ungradable images were present in 3.4% of ETDRS photos versus 31.8% of ARIS images. Exact agreement and agreement within one level between ETDRS photos and ARIS images using only completely gradable image sets occurred in 69% (κ=0.81) and 90% of cases, respectively. Exact agreement for clinically significant macular edema was 92.1% (κ=0.59). There was 100% agreement for eyes with high-risk proliferative DR. Within one level of DR severity, 100% agreement occurred for the following: questionable nonproliferative DR (NPDR), moderate NPDR, and severe NPDR. CONCLUSIONS Results suggest that semiautomated ARIS images compare favorably with ETDRS photos when full image sets can be obtained; however, partially ungradable image sets occurred almost 10 times more frequently with ARIS images than with ETDRS photos. In the two-thirds of cases where ARIS images can be utilized, ARIS can obtain retinal images comparable to ETDRS photos while requiring less highly trained personnel than generally needed for standard ETDRS photos.

Bilateral Candida albicans endophthalmitis associated with an infected deep venous thrombus

BackgroundTo describe the clinical and histopathologic findings in a patient with bilateral Candida albicans endophthalmitis due to an infected deep venous thrombus.CaseA 43-year-old patient with bilateral Candida albicans endophthalmitis due to an infected central venous thrombus. The patient’s ophthalmology and hospital charts were reviewed. Histopathologic sections of the Candida albicans retinal granuloma were examined under light microscopy.ObservationsOur patient had multiple blood cultures positive for Candida albicans owing to an infected subclavicular venous thrombosis. Bilateral Candida albicans endophthalmitis was diagnosed. Bilateral vitrectomy and membrane peeling for macular traction retinal detachments were performed. In the right eye, a large retinal granuloma was excised during surgery to adequately relieve traction on the macula. Vision improved in both eyes after surgery. Histopathologic findings revealed branching hyphae surrounded by giant cells, endothelial cell-lined vascular channels, and inflammatory cells.ConclusionsThis is the first report of an infected deep venous thrombosis causing bilateral endogenous endophthalmitis. Appropriate management of these patients requires clear differentiation between endogenous chorioretinitis and endophthalmitis. Patients with documented fungemia should have a dilated fundus examination on a regular basis until complete clearance of the infection. Jpn J Ophthalmol 2004;48:30–33

Cataract Surgery in Patients with Diabetes: Management Strategies

ABSTRACT Diabetes is a chronic systemic disease that affects nearly one in eight adults worldwide. Ocular complications, such as cataract, can lead to significant visual impairment. Among the worldwide population, cataract is the leading cause of blindness, and patients with diabetes have an increased incidence of cataracts which mature earlier compared to the rest of the population. Cataract surgery is a common and safe procedure, but can be associated with vision-threatening complications in the diabetic population, such as diabetic macular edema, postoperative macular edema, diabetic retinopathy progression, and posterior capsular opacification. This article is a brief review of diabetic cataract and complications associated with cataract extraction in this population of patients.