Patrick Ma

Stage specificity of novel growth factor expression during development of proliferative vitreoretinopathy.

ObjectiveTo compare the relative levels of connective tissue growth factor (CTGF), platelet-derived growth factor alpha (PDGF-AA), and hepatocyte growth factor (HGF) in glial and retinal pigment epithelial (RPE) cells of epiretinal membranes from proliferative vitreoretinopathy (PVR).MethodsA total of 37 PVR membranes, of various stages, underwent fluorescent immunohistochemisty and confocal laser scanning microscopy to localize CTGF, HGF, and PDGF-AA in RPE and glial cells.ResultsNumerous RPE, and relatively fewer glial cells, were found in all stages of PVR. CTGF immunoreactivity increased from early to late stage PVR and was principally expressed by RPE cells in early stage, and by glial cells in late stage PVR. HGF, expressed by both RPE and glial cells, was principally expressed in mid-stage PVR. PDGF-AA, expressed by both cell types, demonstrated a uniform level of staining throughout all stages of PVR.ConclusionsRPE and glial cells contribute to the expression of CTGF, HGF, and PDGF-AA during PVR, but with specific developmental patterns. PDGF-AA is expressed uniformly throughout all stages of PVR, while HGF expression peaks during mid stage, and CTGF expression is highest during late stage PVR. These results allow for the development of stage-specific therapeutics for PVR that may allow targeting of the early proliferative and/or the late tractional stages of PVR.

Sensitivity and specificity of the optos optomap for detecting peripheral retinal lesions.

Purpose: To compare the sensitivity and specificity of the Optomap Panoramic200 wide-field confocal scanning laser imaging system for detecting peripheral retinal lesions. Methods: Optomap images were obtained in patients with known retinal pathology. Two masked retinal specialists evaluated Optomap images to identify lesions requiring referral to a retinal specialist. Their performance was compared to gold standard examination with scleral indentation performed by a retinal specialist. Sensitivity was calculated overall and again for lesions that were found on clinical examination to require treatment. These sensitivities were calculated separately for lesions posterior and anterior to the equator. Specificity was calculated from fellow eyes that were found to have no pathology on clinical examination. Results: For retinal lesions posterior to the equator, sensitivity was 74% (95% confidence interval [95% CI] 61%–87%) overall for all lesions and 76% (95% CI 59%–93%) for lesions requiring treatment. For anterior lesions, sensitivity was 45% (95% CI 28%–62%) overall and 36% (95% CI 14%–58%) for treatable lesions. Specificity was 85% (95% CI 63%–100%). Conclusions: The Optomap showed high specificity and moderate sensitivity for lesions posterior to the equator and low sensitivity for lesions anterior to the equator.

Contribution of Vitreous Cytology to Final Clinical Diagnosis: Fifteen-Year Review of Vitreous Cytology Specimens from One Institution

PURPOSE To assess the contribution of vitreous cytologic evaluation to the diagnosis of clinically undiagnosed vitritis. DESIGN Retrospective chart review and database study. PARTICIPANTS Two hundred seventy-eight eyes of 255 patients who had diagnostic vitrectomies. METHODS We performed a retrospective review of all patients who had vitreous cytology specimens between October 1990 and October 2005 at Vancouver General Hospital. We reviewed the patient charts to obtain the results of microbial and other laboratory testing and to determine the follow-up course. MAIN OUTCOME MEASURES Categories of vitreous cytology specimen results and final clinical diagnosis in patients who had diagnostic vitrectomy specimens. RESULTS We reviewed vitreous cytology results from diagnostic vitrectomies in 278 eyes of 255 patients. One patient had 3 diagnostic vitrectomies, 21 patients had 2 procedures, and 233 patients had a single procedure. We categorized the results of vitreous cytologic examination into 6 major categories: acute inflammation consistent with endophthalmitis (n = 33), primary intraocular lymphoma (PIOL; n = 14), granulomatous inflammation (n = 41), mixed chronic nonspecific inflammation (n = 76), hypocellular specimens (n = 50), and miscellaneous specimens (n = 64). We determined that cytologic diagnosis aided or confirmed a clinical diagnosis, or ruled out PIOL, in 126/228 (55.3%) specimens where patients were not lost to follow-up. CONCLUSIONS Cytologic analysis of vitreous specimens in clinically undiagnosed vitritis is a useful procedure, particularly in the diagnosis of endophthalmitis and PIOL. It is also helpful in confirming granulomatous, nonspecific, and miscellaneous clinical diagnoses and in ruling out PIOL. In this series, it helped to suggest or confirm a diagnosis in the majority of our specimens.

The effects of intravitreal bevacizumab on patients with macular edema secondary to branch retinal vein occlusion

OBJECTIVE To evaluate the effect of intravitreal bevacizumab on visual acuity (VA) and central retinal thickness (CRT) in patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO). DESIGN Retrospective review. PARTICIPANTS The study included 42 patients with ME secondary to BRVO who received intravitreal injections of bevacizumab in 2 referral-based retinal practices in Vancouver, B.C., between November 2005 and July 2006. METHODS We performed a retrospective review of consecutive patients with ME secondary to BRVO. All of the patients in this study had nonischemic BRVOs. Patients were all treated with at least 1 bevacizumab injection and were seen at 6- to 8-week intervals for VA testing. Most of the patients also underwent optical coherence tomography (OCT) 2 months and 6 months after treatment. VA and OCT measurements at each follow-up time point were compared with the baseline values. RESULTS A total of 42 eyes from 42 patients with ME secondary to BRVO were reviewed. The mean VA improved from 20/280 at baseline to 20/180 at first follow-up session (p < 0.04; average follow-up = 42 days) and remained at a similar level, 20/170, through the eighth follow-up session (p < 0.04; average follow-up = 356). The CRT was reduced from a mean of 451 microm (388-512 microm) at baseline to 358 microm (298-418 microm) at 2 months (p < 0.02) and to 400 microm (335-465 microm) at 6 months postinjection (p < 0.068). CONCLUSIONS We found a significant improvement in VA and CRT in patients with ME secondary to BRVO after intravitreal bevacizumab injection(s). No complications or serious side effects were observed. Intravitreal bevacizumab appears to have an emerging role as either a primary or an adjuvant treatment modality in the setting of ME secondary to BRVO.

Ranibizumab Is a Potential Prophylaxis for Proliferative Vitreoretinopathy, a Nonangiogenic Blinding Disease

Proliferative vitreoretinopathy (PVR) exemplifies a disease that is difficult to predict, lacks effective treatment options, and substantially reduces the quality of life of an individual. Surgery to correct a rhegmatogenous retinal detachment fails primarily because of PVR. Likely mediators of PVR are growth factors in vitreous, which stimulate cells within and behind the retina as an inevitable consequence of a breached retina. Three classes of growth factors [vascular endothelial growth factor A (VEGF-A), platelet-derived growth factors (PDGFs), and non-PDGFs (growth factors outside of the PDGF family)] are relevant to PVR pathogenesis because they act on PDGF receptor α, which is required for experimental PVR and is associated with this disease in humans. We discovered that ranibizumab (a clinically approved agent that neutralizes VEGF-A) reduced the bioactivity of vitreous from patients and experimental animals with PVR, and protected rabbits from developing disease. The apparent mechanism of ranibizumab action involved derepressing PDGFs, which, at the concentrations present in PVR vitreous, inhibited non-PDGF-mediated activation of PDGF receptor α. These preclinical findings suggest that available approaches to neutralize VEGF-A are prophylactic for PVR, and that anti-VEGF-based therapies may be effective for managing more than angiogenesis- and edema-driven pathological conditions.

Induction of proliferative vitreoretinopathy by a unique line of human retinal pigment epithelial cells

BACKGROUND The most widely used models of proliferative vitreoretinopathy (PVR) rely on injection of cells into the vitreous of animals. Using retinal pigment epithelial (RPE) cells from human PVR membranes may produce a more accurate model of human PVR. We performed a study to determine whether human RPE cells derived from a single epiretinal membrane (ERM) are capable of inducing the same disease in the rabbit eye, and whether the induced ERMs had cellular components similar to those of human PVR membranes. METHODS Cells were harvested from a human ERM obtained at surgery for PVR. RPE cells were cultured from the membrane and injected into the right eye of 24 New Zealand albino rabbits. The left eyes served as controls. The eyes were examined by indirect ophthalmoscopy over 4 weeks. The enucleated eyes were then examined by means of microscopy and histochemical analysis. RESULTS By day 7, PVR had developed in all but 1 of the 24 experimental eyes, with 8 progressing to localized tractional retinal detachment. By day 21, localized tractional retinal detachment had developed in 17 eyes; 1 eye progressed to extensive tractional retinal detachment by day 28. Immunostaining showed that mostly RPE cells, but also myofibroblasts, glial cells and collagen, were present in the newly formed rabbit PVR membranes. INTERPRETATION Human RPE cells cultured from a PVR membrane appear to be capable of inducing PVR in rabbits. The resultant ERMs are similar to those formed in human PVR and consist mainly of RPE cells.

Technique for removal of a capsular tension ring from the vitreous

PURPOSE To report a new technique for safely and quickly removing a displaced capsular tension ring from the vitreous cavity. DESIGN Two interventional case reports. PARTICIPANTS The authors retrospectively reviewed the charts of two patients with displaced capsular tension rings (CTRs). INTERVENTION Surgical removal of the displaced CTRs was performed in two patients. MAIN OUTCOME MEASURES Visual and anatomic outcomes. RESULTS The CTRs were removed surgically, in case 1 by cutting the CTR into two pieces before removal and in case 2 by using the CTR injector to remove the CTR in one piece through a sclerotomy site. Both patients had good visual and anatomic outcomes. CONCLUSIONS The described technique of removing a displaced CTR in one piece through a sclerotomy site using the CTR injector provides a safe and efficient method of CTR removal. Cutting the CTR into two or more pieces for removal is not recommended.

Expression of integrins in human proliferative diabetic retinopathy membranes.

BACKGROUND The process of identifying molecules that regulate angiogenesis is critical to the success of candidate therapies for ocular neovascular disease. The purpose of the study was to determine the pattern of expression for integrins and their colocalization with endothelium in membranes from proliferative diabetic retinopathy (PDR). METHODS Clinically categorized membranes were collected from vitreoretinal surgery. A double immunohistochemical staining procedure was used to identify the presence and colocalization of integrins and endothelium. Five integrins were examined. RESULTS Endothelial markers were robust in all 4 active-stage PDR membranes but absent in the fibrotic-stage PDR membrane. The expression of alpha;vbeta3 and beta3 integrins on endothelial cells was observed with low to moderate intensity. The expression of alpha;1beta1 and alpha;2beta1 was moderate but was not colocalized with endothelial cells in active-stage PDR membranes. Integrin alpha;vbeta5 was not evident in any of the samples used in this study. INTERPRETATION The results suggest an essential role of integrins alpha;vbeta3 and beta3 in the pathogenesis of PDR. It is suggested that alpha;vbeta3 and beta3 are preferred candidate targets for therapeutic development.

Comparison of photodynamic therapy and transpupillary thermotherapy for subfoveal choroidal neovascularization due to age-related macular degeneration

BACKGROUND The purpose of this study was to compare photodynamic therapy (PDT) against subthreshold transpupillary thermotherapy (TTT) with a diode laser for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). METHODS Patients with subfoveal choroidal neovascularization secondary to AMD were offered PDT as an initial intervention. If they declined PDT, then TTT was offered. RESULTS We evaluated and followed 115 consecutive patients for an average of 1 year. The primary outcome measure was visual acuity, but the interventions were also compared on the basis of lesion size and angiographically determined lesion activity. Baseline comparisons between the 2 treatment groups showed significant differences in pretreatment visual acuity, lesion size, and lesion composition. Univariate analysis of outcomes demonstrated equivalence between the treatment groups in final lesion size, angiographic activity, and visual acuity. Multivariate analysis also demonstrated equivalence between the treatment groups in final visual acuity while controlling for age, pretreatment visual acuity, and lesion category. Predominantly classic lesions were associated with poorer visual outcomes. INTERPRETATION The PDT and TTT groups were equivalent in terms of all outcome parameters evaluated.

Socioeconomic status and clinical features of patients undergoing photodynamic therapy or transpupillary thermotherapy for subfoveal choroidal neovascularization due to age-related macular degeneration.

BACKGROUND The purpose of this study was to compare baseline clinical and socioeconomic features of patients undergoing self-funded photodynamic therapy (PDT) or government-funded subthreshold transpupillary thermotherapy (TTT) with a diode laser for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). METHODS Between July 2000 and August 2001, 115 patients with subfoveal choroidal neovascularization secondary to AMD were offered PDT as an initial intervention. If individuals believed that they could not afford or did not want PDT, then TTT was offered. In masked fashion, leakage pattern and lesion size were determined retrospectively from pretreatment angiograms. Baseline visual acuity was determined with autorefraction and subsequent Snellen testing. The mean income of each treatment group was estimated from the average sex-specific income for each subjects postal code, based on the 1996 Canadian census data. The average education level for each subjects postal code was also determined. RESULTS The patients who were not willing to pay for PDT had significantly worse macular disease before treatment (larger lesions and poorer visual acuity) and a significantly lower mean income than the patients who were willing to pay for PDT. INTERPRETATION The severity of exudative choroidal neovascularization appears to be associated with lower socioeconomic status.