Stefan Seregard

Cut and paste: a no suture, small incision approach to pterygium surgery

Aim: Evaluation of the benefits of a new technique for pterygium surgery with respect to postoperative pain and surgery time. Methods: A prospective randomised clinical trial was carried out in 43 patients. 43 eyes were operated for primary nasal pterygium. Autologous conjunctival graft taken at the superotemporal limbus was used to cover the sclera after pterygium excision. After randomisation, in 20 patients the transplant was attached to the sclera with a fibrin tissue adhesive (Tisseel Duo Quick) and in 23 patients with absorbable sutures (7–0 Vicryl Rapid). The Mann-Whitney test was used as statistical analysis. Postoperative pain was graded according to the visual analogue scale (VAS) twice daily during the first week after surgery. Surgery time was noted from the first incision until the lid speculum was removed. Results: The average pain was significantly lower when glue had been used, p<0.05. Average surgery time was 9.7 minutes (range 6–13) for glue and 18.5 minutes (range 12–30) for sutures, p<0.001. No complications occurred. Conclusion: Using glue instead of sutures when attaching the conjunctival transplant in pterygium surgery causes significantly less postoperative pain and shortens surgery time significantly.

The Insulin-Like Growth Factor-I Receptor Inhibitor Picropodophyllin Causes Tumor Regression and Attenuates Mechanisms Involved in Invasion of Uveal Melanoma Cells

PURPOSE: Uveal melanoma has a high mortality rate due to a high incidence of metastasis (up to 50%), which preferentially occurs in the liver. Conventional chemotherapy, being the only therapeutic option today against metastatic uveal melanoma, has not proved to be effective. Therefore, new molecular targets important for malignant phenotype of uveal melanoma have to be found to design efficient pharmacologic agents. EXPERIMENTAL DESIGN: We previously reported data indicating that the insulin-like growth factor-1 receptor (IGF-IR) is a metastasis predictor as well as a therapeutic target for uveal melanoma. In the present study, we made use of the cyclolignan picropodophyllin (PPP), which is an inhibitor of the IGF-IR. RESULTS: We showed that PPP efficiently blocks growth and viability of uveal melanoma cells in cultures and causes tumor regression in xenografted mice. In addition, treatment with PPP inhibited several mechanisms involved in metastasis, including tumor cell adhesion to extracellular matrix proteins, activity and expression of matrix metalloproteinase 2, and cell migration as well as invasion through basement membranes and endothelial cell layers. Furthermore, PPP significantly delayed establishment of uveal melanoma tumors and drastically reduced the incidence of liver metastasis in mice. CONCLUSIONS: Our data suggest that IGF-IR is crucial for growth and survival as well as invasion and metastasis of uveal melanoma cells. Targeting this receptor may therefore comprise a strategy to treat ongoing disease (today incurable) as well as a strategy to prevent development of metastases in patients with primary disease.

Prognostic accuracy of the mean of the largest nucleoli, vascular patterns, and PC-10 in posterior uveal melanoma

OBJECTIVE This study aimed to compare the prognostic value and the predictive accuracy of the PC-10 cell cycling marker with the largest tumor diameter, the mean of the largest nucleoli, and vascular patterns in posterior uveal melanoma. DESIGN The study design was a case-control study. PARTICIPANTS Eyes enucleated for posterior uveal melanoma from patients who either died of metastatic melanoma or survived without signs of metastatic disease 10 years or more after surgery were studied. INTERVENTION Three observers assessed the above prognostic indicators and standard histopathologic characteristics from microslides without access to survival data. MAIN OUTCOME MEASURES Univariate and multivariate Cox models for survival were constructed, and a multiparameter prognostic index was calculated for each patient, based on covariates obtained from the final Cox model. The prognostic accuracy was determined by receiver operating characteristic curve analysis. RESULTS The log PC-10 count, vascular networks, mean of the largest nucleoli, largest tumor diameter, age of patient, and prognostic index were independently associated with outcome. However, each of these indicators had no more than a poor-to-moderate predictive accuracy, and only the prognostic index was significantly better than the largest tumor diameter. CONCLUSIONS The PC-10 count retains a prognostic value in uveal melanoma when adjusting for the effect of the mean of the largest nucleoli and diverse vascular patterns. A prognostic index combining two or more indicators may improve the predictive precision.

Immunohistochemical characterization of surgically removed subfoveal fibrovascular membranes

Eighteen patients with age-related macular degeneration developed subfoveal membranes that were surgically removed and submitted for histopathological examination. Immunohistochemical techniques were performed, using a panel of monoclonal antibodies recognizing retinal pigment epithelial (RPE) cells, myofibroblasts, pericytes, endothelial cells, glial cells, smooth muscle cells and various types of macrophages. The PC10 antibody to proliferating cell nuclear antigen (PCNA) was applied as a marker of proliferating cells. The specimens displayed a core of neovascular stroma surrounded by a rim of more fibrous tissue. All specimens contained abundant RPE cells that in some cases appeared to envelop part of the membrane. Most cases had basal laminar deposits and thickened basement membrane material adjacent to the RPE cells suggestive of parts of Bruchs membrane. Often this Bruchlike membrane appeared at the surgical margin, forming a surgical cleavage plane. Chronic inflammatory cells were abundant, but polymorphonuclear leukocytes were notably absent. Nearly all specimens contained myofibroblasts and various types of macrophages. The presence of myofibroblasts suggests subretinal membrane contraction, which may induce new breaks and other pathology in RPE layer and Bruchs membrane.

Conjunctival malignant melanoma in Sweden 1969-91.

Abstract. Clinical information, follow‐up and histopathological parameters of the primary lesions were assessed for all (45) individuals with conjunctival malignant melanomas in Sweden presenting during a 22.5 year period (1969 to mid 1991). The annual incidence of conjunctival malignant melanoma in Sweden was 0.0240 per 100 000. On average, two new cases were diagnosed each year (population 8.6 million in 1991). Sixty‐two per cent of the lesions recurred, but re‐growth in itself was not correlated to reduced survival. The actuarial 10‐year survival proportion using life‐table analysis was 70%. A significantly reduced survival due to tumour‐related death was noted in patients with tumours with high mitotic indices, many epitheloid cells and in lesions exceeding 10 mm in diameter. Other factors that may influence survival are presented in the context of previous reports. The present policy in Sweden for treating patients with malignant melanoma of the conjunctiva is outlined and discussed.

A prospective study on intravitreal bevacizumab (Avastin®) for neovascular age‐related macular degeneration of different durations

Purpose:  Choroidal neovascularization (CNV) accounts for 85–90% of severe visual impairment in age‐related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a major factor mediating angiogenesis, and VEGF inhibitors have become a new treatment modality. In this prospective study, we used bevacizumab (Avastin®), a recombinant monoclonal antibody to VEGF, to treat neovascular AMD.

Benefit from Bevacizumab for Macular Edema in Central Retinal Vein Occlusion: Twelve-Month Results of a Prospective, Randomized Study

PURPOSE To evaluate the efficacy of intraocular injections with bevacizumab over 12 months in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). DESIGN A prospective study including a randomized 6-month, sham injection-controlled, double-masked clinical trial followed by a 6-month open-label extension. PARTICIPANTS Sixty patients with ME secondary to CRVO. METHODS At baseline, patients were randomized 1:1 to receive intraocular injections of bevacizumab or sham injections every 6 weeks for 6 months. From month 6, all patients received intraocular injections of bevacizumab every 6 weeks for 6 months. MAIN OUTCOME MEASURES The primary outcome measure was the proportion of patients gaining at least 15 letters at 12 months. Secondary outcome measures included mean change from baseline best-corrected visual acuity (BCVA), change in foveal thickness, and development of neovascular glaucoma. RESULTS At the end of follow-up, 18 of 30 patients (60.0%) in the bevacizumab/bevacizumab (bz/bz) group had gained ≥ 15 letters compared with 10 of 30 patients (33.3%) in the sham/bevacizumab (sh/bz) group (P < 0.05). The BCVA improved by 16.0 letters at 12 months in the bz/bz group compared with 4.6 letters in the sh/bz group (P < 0.05). In an unplanned retrospective analysis, patients aged >70 years had a significantly worse outcome when receiving delayed treatment, losing 1.4 letters (95% confidence interval [CI], -9.7 to 8.4) in the sh/bz group compared with a gain of 20.1 letters (95% CI, 13.9-26.3) in the bz/bz group in patients aged <70 years (P < 0.003). The mean decrease in central retinal thickness (CRT) was 435 μm in the bz/bz group compared with 404 μm in the sh/bz group (P = not significant). No patients developed iris rubeosis during the 6-month open-label extension period. There were no events of endophthalmitis, retinal tear, or retinal detachment during the 12-month treatment period. No serious nonocular adverse events were reported. CONCLUSIONS Intraocular injections of bevacizumab given every 6 weeks for 12 months improve visual acuity (VA) and reduce ME significantly. Patients receiving delayed treatment have a limited visual improvement. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Bevacizumab for Macular Edema in Central Retinal Vein Occlusion: A Prospective, Randomized, Double-Masked Clinical Study

PURPOSE To evaluate the efficacy of intraocular injections with bevacizumab in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). DESIGN Prospective, randomized, sham injection-controlled, double-masked clinical trial. PARTICIPANTS Sixty patients with ME secondary to CRVO. METHODS At baseline, patients were randomized 1:1 to receive intraocular injections of bevacizumab or sham injections every 6 weeks for 6 months. MAIN OUTCOME MEASURES The primary outcome measure was the proportion of patients gaining at least 15 letters at 6 months. Secondary outcome measures included mean change from baseline best-corrected visual acuity (BCVA), foveal thickness, and neovascular glaucoma. RESULTS At the end of follow-up, 18 of 30 patients (60.0%) in the study group had gained ≥15 letters compared with 6 of 30 patients (20.0%) in the control group (P=0.003). The BCVA improved by 14.1 letters at 24 weeks compared with a decrease of 2.0 letters in the control group (P < 0.003). The mean decrease in central retinal thickness (CRT) was significantly greater in the study group (426 μm) than in the control group (102 μm) at all time points up to week 24 (P < 0.001). No residual edema, defined as CRT <300 μm at 24 weeks, was found in 26 of 30 patients (86.7%) in the treatment group compared with 6 of 30 patients (20%) in the control group (P < 0.001). In the sham group, 5 of 30 patients (16.7%) had developed iris rubeosis at week 24. No patients in the study group had rubeosis at week 24 (P=0.052). There were no events of endophthalmitis, retinal tear, or retinal detachment during the 24-week treatment period. No serious non-ocular adverse events were reported. CONCLUSIONS Intraocular injections of bevacizumab given every 6 weeks for 6 months improve visual acuity (VA) and reduce ME significantly compared with sham. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Photoreceptor decay over time and apoptosis in experimental retinal detachment

Background: Data are scarce on the actual rate and mode of outer nuclear layer decay in retinal detachment (RD). We used an experimental rabbit model to assess the presence of apoptosis and rate of photoreceptor death following RD. This model included the creation of localized and stable retinal blebs, while controlling for any decline of retinal elevation over time.Methods: RD was produced in New Zealand white rabbits by injecting 0.05 ml of 15% sodium hyaluronate (Healon GV) under the neural retina using a microsurgical technique. Animals were killed at 1, 2, 4, 7, 14 and 29 days. Retinal tissue was processed for light and electron microscopy and for in situ end labeling of fragmented DNA using a modification of the TUNEL technique. Photoreceptor cell nuclei were counted in the RD areas of maximum retinal elevation of 28 eyes, and an additional 4 eyes were used for nick end labeling.Results: Positive DNA nick end labeling, ultrastructural features and absence of necrotic cells indicated apoptotic photoreceptor cell death. Also, there was a rapid, almost linear elimination of photoreceptor nuclei over time. At 14 days only half of the number of nuclei were discernible, while approximately one tenth remained after 29 days. There was a statistically significant, but minimal decline in RD height over the 4 weeks of study.Conclusion: Following experimental RD in rabbits, apoptotic cell death is associated with an almost linear elimination of photoreceptor cells over time. The use of highly viscous sodium hyaluronate in separating the neural retina from the retinal pigment epithelium allows the RD to maintain a nearly constant height over a period of 4 weeks.

Matrix metalloproteinase (MMP) expression in experimental choroidal neovascularization

PURPOSE Matrix metalloproteinases (MMP) are a family of proteolytic enzymes that degrade basement membrane and extracellular matrix proteins. To gain information on the possible role of MMPs in choroidal neovascularization (CNV), we have analyzed the mRNA expression of MMP-2 and MMP-9, two forms of MMPs implicated in ocular neovascularization, in a rat model. METHODS Choroidal neovascularization was induced in pigmented rats by krypton laser photocoagulation of the fundus whereafter eyes were enucleated at 1, 3, 5, 7, 10 and 60 days. Antisense and sense riboprobes were generated using DNA complementary to MMP-2 and MMP-9, and mRNA expression was analyzed using in situ hybridization. RESULTS In the untreated eyes MMP-2 mRNA expression was weakly detected in cells within the choroid. In laser-treated eyes MMP-2 mRNA expression was markedly increased and mainly localized to macrophage-like and retinal pigment epithelial (RPE)-like cells invading the choroid, subretinal space and inner retina. This increase in MMP-2 mRNA expression peaked at day 10 whereafter a decline was detected. MMP-9 mRNA expression was low in untreated eyes and did not increase following laser treatment. CONCLUSION The results show that MMP-2 mRNA expression is increased in experimental CNV, and support of a role for MMP-2 in the development of CNV in age-related macular degeneration.