Efficacy of plasmin enzymes and chondroitinase ABC in creating posterior vitreous separation in the pig: a masked,placebo-controlled in vivo study

Background Induction of posterior vitreous detachment (PVD) during vitrectomy helps to prevent proliferative complications, but can be traumatic to the retina, particularly in young patients. Adjunct enzymes have been proposed to facilitate PVD. We investigated the efficacy of enzymes in creating PVD as an adjunct to vitrectomy in the pig. Methods Five groups of 8 pigs received a masked intravitreal injection of chondroitinase (1 IU), human (0.4 or 1.3 activity units [AU]) or porcine plasmin (0.18 AU or 0.47 AU) into one eye, and osmolarity adjusted control into the other. After incubation, a core vitrectomy was performed on each eye at low suction, without vitreous peeling. The occurrence of spontaneous PVD and its extent were graded. Eyes were investigated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Vitreous remnants on the retina were quantified in SEM. Data were analyzed using McNemar’s test for paired observations and Wilcoxon paired signed rank test. Results Spontaneous PVD occurred more frequently in human plasmin-treated eyes (p<0.025) and all plasmin eyes (p<0.025) than in placebo controls. The extent of PVD appeared larger in human plasmin (p<0.025) and all plasmin-treated eyes (p<0.025). In plasmin-treated eyes, SEM morphometry showed a significant reduction in the vitreous-covered retina areas. Chondroitinase failed to produce an effect. Conclusions Plasmin may prove a useful adjunct to conventional vitrectomy. The results were presented in part at the ARVO Annual Meeting, 2001.     

Safety profile of the intravitreal streptokinase-plasmin complex as an adjunct to vitrectomy in the rabbit

Background The generation of an atraumatic posterior vitreous detachment (PVD), a common goal in vitreoretinal surgery, is a challenge, particularly in children and young trauma patients. Plasmin has been proposed as an adjunct to vitrectomy to enzymatically generate a PVD. Low doses of streptokinase-activated plasmin were tested in human pilot studies. This dose-escalation study assesses the safety range of intravitreal human streptokinase-plasmin in rabbits.Methods Plasminogen was isolated from human plasma by affinity chromatography, followed by activation with streptokinase (1:1), to generate the streptokinase-plasmin complex. Enzyme doses from 0.1–7 activity units (AU, in 0.1 ml) were injected into the mid-vitreous of 35 eyes; six control eyes were injected with balanced salt solution (BSS, 0.1 ml). Thirty minutes after injection, a two-port vitrectomy was performed. Fundus and slit lamp examinations were performed on days 1 and 7. On days 2 and 7, bright flash electroretinography was performed and compared with preoperative recordings. Some animals receiving higher doses of streptokinase-plasmin (1–7 AU) were followed clinically and with electroretinography for up to 9 months.Results A mild-to-moderate inflammatory response was seen in both control and plasmin-treated eyes on day 1, but had disappeared completely by day 7 in most eyes. In the 7 AU group, inflammation was stronger and more protracted. Two of three eyes from this group developed wrinkling of the medullary rays; one of them showed discoloration and traction at the medullary rays in the late follow-up.Electroretinograms (ERGs) of vitrectomized control eyes showed the following changes from preoperative values: 48 h, a-wave −11.10% [no significant (n.s.)], b-wave −14.62% (P=0.046); 7 days, a-wave +9.18% (n.s.), b wave +11.69% (n.s.). For the enzyme-treated eyes: 48 h: a-wave −20.43% (P<0.001), b-wave −9.57% (p<0.001); 7 days: a wave −14.21% (P<0.001), b-wave +2.48% (P<0.001).There was no evidence of dose-dependent ERG changes in enzyme-treated eyes at doses up to 5 AU. Groups of up to 3 AU were investigated by light and transmission electron microscopy, without evidence of toxicity.Conclusion Streptokinase-plasmin doses up to 3 AU were found to be safe when injected into rabbit eyes followed by vitrectomy.This work was presented in part at the 74th Annual Meeting of the Association for Research in Vision and Ophthalmology, 2002.     

Peeling of internal limiting membrane during vitrectomy for complicated retinal detachment prevents epimacular membrane formation

Background  To investigate the clinical benefit of internal limiting membrane (ILM) peeling at the macula for the prevention of epimacular membrane formation following vitreous surgery using silicone oil for the treatment of complicated retinal detachment. Methods  This was a non-randomized, retrospective, interventional study of a case series. Patient charts were reviewed retrospectively for 20 consecutively recruited patients who underwent successful primary vitrectomy with ILM peeling at the macula using silicone oil (group 1) and 22 consecutively recruited patients who underwent successful primary vitrectomy using silicone oil without ILM peeling at the macula for complicated rhegmatogenous retinal detachment (group 2). The main outcome measures were distant visual acuity and epimacular membrane formation. The data were analyzed and compared using Fisher’s Exact test, Pearson Chi-square test, independent t-test, Mann–Whitney U-test, and a repeated ANOVA. Results  The mean age of patients was 52.7 ± 12.6 years in group 1 and 53.2 ± 13.3 years in group 2 (p = 0.89). The mean follow-up time was 24.6 ± 7.6 weeks in group 1 and 34.1 ± 12.6 weeks in group 2 (p = 0.01). Preoperatively, ten eyes in group 1 and 10 eyes in group 2 were pseudophakic; the macula was detached in all cases. Silicone oil had been removed from all eyes of both groups at least 3 months before the final examination. There were no significant differences between the two groups with regard to sex (p = 0.44), mean duration of retinal detachment (p = 0.12), mean preoperative visual acuity (logMAR), mean number of retinal breaks (p = 0.43), and grade of proliferative vitreoretinopathy (p = 0.35). The final visual acuity (logMAR) was 0.60 ± 0.30 in group 1 and 0.72 ± 0.35 in group 2 (p = 0.49). Four eyes in group 1 and two eyes in group 2 underwent cataract surgery during silicone oil removal. Epimacular membrane formation was observed in two eyes before silicone oil removal and in four eyes within 8 weeks after silicone oil removal in group 2. No epimacular membrane formation was seen in group 1 (p = 0.02). Conclusion  ILM peeling at the macula during vitreous surgery with silicone oil for the treatment of complicated retinal detachment may prevent epimacular membrane formation without negatively affecting distant visual acuity. The results of this study were presented at the 8th Euretina Congress 2008, Vienna, Austria. The authors have no conflicting interests in the subject matter presented.     

Management of postvitrectomy diabetic vitreous hemorrhage with volume homeostatic fluid-fluid exchanger

Background  To evaluate the clinical outcome of patients with postvitrectomy diabetic vitreous hemorrhage (PDVH) who underwent vitreous cavity lavage (VL) by volume homeostatic fluid–fluid exchange. Methods  We performed a retrospective chart review for 88 eyes of 80 consecutive patients who underwent VL for PDVH. Final best-corrected visual acuity after VL was compared to those before VL. Anatomic outcome, including rate of fundus clear-up, recurrent vitreous hemorrhage, increased intraocular pressure, iris neovacularization and anterior hyaloid fibrovascular proliferation were considered. Results  Between July 1999 and January 2006, 88 eyes of 80 patients underwent this procedure. Significant visual improvement was observed after VL (2.86 ± 0.40 logMAR at baseline vs 1.71 ± 0.97 logMAR at last visit, p < 0.0001). The fundus clear-up rate after VL was achieved in 84 out of 109 times (77.1%). Recurrent vitreous hemorrhage was found in 17 of 88 eyes (19.3%) with the mean interval of 92.6 ± 126.7 days after VL. Conclusions  For patients suffering from postvitrectomy diabetic vitreous hemorrhage, volume homeostatic vitreous cavity lavage can be an alternative method for removing the bloody content in the vitreous cavity efficiently and permitting rapid visual recovery.     

Preoperative B-scan ultrasonography of the vitreoretinal interface in phakic patients undergoing rhegmatogenous retinal detachment repair and its prognostic significance

Purpose To perform ultrasonographic evaluation of the preoperative status of the posterior vitreoretinal interface in phakic patients undergoing surgery for retinal detachment (RD) with flap tear(s) and to investigate its relationship with postoperative anatomic and visual acuity outcomes. Methods A prospective, consecutive case series including 50 phakic eyes of 49 patients with retinal detachment and flap tear(s) undergoing retinal detachment surgery by a single vitreoretinal surgeon, who was unaware of the patient’s preoperative B-scan ultrasonographic findings. Main outcome measures were comparisons between patients with partial versus complete posterior vitreous detachment (PVD) of primary retinal reattachment rates (retinal reattachment with a single surgical procedure), rates of retinal reattachment at month 12, and visual acuity outcomes at month 12. Results Partial PVD was observed in 22 (44%) eyes and complete PVD in 28 (56%) eyes. Eighteen eyes underwent pneumatic retinopexy, 15 underwent scleral buckling, and 17 underwent pars plana vitrectomy. Retinal reattachment with a single surgical procedure was achieved in 76% (38/50) of eyes, including 54.5% (12/22) of eyes with partial PVD at baseline and 92.9% (26/28) of eyes with complete PVD at baseline (P < 0.01). Stratification by type of surgical intervention demonstrated a significantly higher rate of primary anatomic success for pneumatic retinopexy among patients with complete PVD compared to partial PVD (P = 0.02). Retinal reattachment at month 12 was achieved in 100% (50/50) of eyes. At last follow-up, the mean (±SD) number of interventions was 1.70 (±1.10) for patients with partial PVD at baseline and 1.10 (±0.30) for patients with complete PVD (P < 0.01). There was no significant difference among the groups in mean change in visual acuity from baseline to month 12, nor in the distribution of visual acuities at month 12. Conclusions In phakic patients with retinal detachment and flap tear(s), a higher primary anatomic success rate may be associated with the presence of a complete PVD compared to a partial PVD. Subgroup analysis suggests that the presence of partial PVD at baseline might influence negatively the primary anatomic success rate, particularly for eyes undergoing pneumatic retinopexy. Presented in part as a paper at the ARVO 2004 Annual Meeting, Fort Lauderdale, FL, and at the American Society of Retina Specialists 2004 Annual Meeting, San Diego, CA. The authors have full access to all the data in the study and agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review our data upon request. Financial interest: F. Rezende, none; M. Kapusta, none; R. Costa, none; I. Scott, none. An erratum to this article can be found at     

Intravitreal bevacizumab in active progressive proliferative diabetic retinopathy

Background  Vitreous concentration of vascular endothelial growth factor (VEGF) rises significantly during proliferative diabetic retinopathy (PDR). Bevacizumab (Avastin) is a humanized monoclonal antibody to VEGF. Intravitreal administration of bevacizumab (IVB) has recently been shown to be effective in some ocular neovascularizations, including PDR. In this study we evaluate the efficacy of IVB in eyes with active, progressive PDR. Methods  In an interventional prospective case series, eyes with active, progressive PDR underwent one to three IVB injections (1.25 mg) at intervals of either 6 or 12 weeks. Complete ophthalmic examinations and color fundus photography were performed at baseline and 1, 6, 12, and 20 weeks after the first injection. Fluorescein angiography (FA) was performed before injection and 20 weeks after. The primary outcome measures were clearing of vitreous hemorrhage (VH) and regression of active fibrovascular tissue (FVT). The secondary outcomes were any change in best-corrected visual acuity (BCVA) and any incidence of adverse events. Results  Thirty eight eyes of 38 patients with a mean age of 54.7 ± 10.1 years were included in the study. VH resolved significantly after 1 week (P = 0.014), 12 weeks (P = 0.0001), and 20 weeks (P = 0.002). The vascular component of FVT regressed, though the FVT area did not change. Mean BCVA improved significantly compared to baseline at all follow-up examinations. Two cases showing moderate fibrous proliferation developed traction retinal detachment (TRD). Conclusions  IVB has significant therapeutic effect on eyes with active, progressive PDR: the treatment causes a significant amount of VH resolution and neovessel regression. At the same time, this procedure may increase the risk of TRD in eyes with fibrous proliferation. The authors have no proprietary interest in this study. The authors have full control of all primary data, and they agree to allow Graefes Archive for Clinical and Experimental Ophthalmology to review their data upon request.     

糖尿病大鼠药物性玻璃体松解术的研究

目的 研究在糖尿病大鼠中能否采用药物性玻璃体松解术诱导完全性玻璃体后脱离(PVD).方法 实验研究.成年SD大鼠用链脲佐菌素(STZ)腹腔注射诱发糖尿病,4周后用视觉电生理、视网膜血管铺片、透射电镜观明确视网膜病变的发生.发病4周后将糖尿病大鼠分为4组:A组10只,右眼玻璃体内注射透明质酸酶5 U;B组10只,右眼玻璃体腔内注射纤溶酶0.5 U;C组10只,右眼玻璃体腔内注射纤溶酶0.5 U+透明质酸酶5 U;D组10只,右眼玻璃体注射BSS 2 μl.注射后一周内观察眼部一般情况并检查视觉电生理变化(F-ERG).一周时取各组大鼠视网膜做扫描电镜检查和组织切片,观察视网膜组织结构及玻璃体后脱离的发生情况.对数据采用t检验进行统计学分析.结果 糖尿病大鼠发病4周时已经有视觉电生理的改变,血管铺片显示周细胞的减少(t=6.1,P<0.01);Ops振幅降低、峰时延迟(t=2.8,3.4;P<0.05);透射电镜显示毛细血管周细胞水肿变性.玻璃体腔注射药物一周后,通过扫描电镜观察A组和D组无PVD发生(0/10);B组发生部分性PVD 6/10,完全性PVD 4/10;C组发生完全性PVD 10/10.视觉电生理检查各组与注射前相比差异均无统计学意义(P>0.05),组织切片检查未显示视网膜组织结构的异常改变.结论 STZ诱导糖尿病4周大鼠视网膜已经出现了病理改变,在其玻璃体腔中注射0.5 U的纤溶酶加5 U的透明质酸酶能够稳定地诱发出完全性PVD,而单独使用纤溶酶仅能诱发出部分性PVD,透明质酸酶不能诱发出PVD.各组未见药物对视网膜的结构和功能造成明显的毒性反应.     

Bevacizumab (Avastin) treatment in patients with retinal angiomatous proliferation

Aim To determine the anatomical and functional outcome after injection of bevacizumab (Avastin, Genentech) in eyes with retinal angiomatous proliferation (RAP). Design Prospective interventional case series. Methods Sixteen eyes of 16 consecutive patients with visual loss due to RAP underwent intravitreal injections of 1.25 mg (0.05 ml) bevacizumab. Best corrected visual acuity testing, fluorescein and ICG-angiography as well as OCT imaging were performed at baseline and at each follow-up visit within a 3-month period. Results Mean visual acuity pre-injection was 0.68 ± 0.36 logMAR (n = 16), mean reading ability 0.58 ± 0.26 logRAD (n = 11). Far vision increased significantly by a mean of 1.7 ± 2 lines 4 weeks after the injection (p = 0.004), as did reading (0.6 ± 2.3 lines, p > 0.05). Both remained stable up to 3 months. Central retinal thickness decreased from 367 ± 112 μm (mean±SD) to 272 ± 123 μm 3 months after injection (p = 0.006). Leakage decreased angiographically in 12 eyes (75%) and remained stable in four eyes (25%). Re-injection of bevacizumab within the 3-month follow-up period was performed once in eight eyes, and twice in one eye. No adverse events were observed. Conclusion Intravitreal bevacizumab (Avastin) resulted in a reduction of leakage, intra- and subretinal fluid. An increase in visual acuity was seen already 4 weeks after first injection. However, a complete occlusion of feeder vessels could not be achieved within this 3-month period. Randomized clinical trials would be required to evaluate dose and frequency of injections and possible beneficial effects of combination therapies, as well as the long-term results.     

纤维蛋白溶解酶诱导兔眼玻璃体后脱离

目的 研究纤维蛋白溶解酶分别联合透明质酸酶和气体六氟化硫(SF-6)诱导兔眼玻璃体后脱离（PVD）的效果。 方法 18只健康成年青紫兰兔随机分为A、B、C 3组，每组6只兔。右眼均为实验眼，左眼为对照眼。A、B、C 组实验眼玻璃体腔内分别注射纤溶酶1 U(浓度10 U/ml)、纤溶酶1 U和透明质酸酶20 U(浓度200 U/ml)、纤溶酶1 U和SF6 0.5 ml；对照眼玻璃体腔内注射眼用平衡盐溶液（BSS）0.1ml。注药前后行间接检眼镜、裂隙灯和VOLK+90D前置镜及B型超声和视网膜电图(ERG)检查。最后取所有兔眼行光学显微镜、扫描电子显微镜和透射电子显微镜观察。 结果 扫描电子显微镜观察结果：A组实验眼中有2只眼后极部发生不完全性PVD，发生率为33.3%；B、C两组实验眼中分别各有4只眼发生完全性PVD，发生率为66.7%；B、C两组实验眼出现PVD的阳性发生率与A组比较，差异有统计学意义 (P<0.05)。3组实验眼注药后ERG振幅与手术前及对照眼比较差异均无统计学意义（P>0.05）。光学显微镜和透射电子显微镜观察结果显示，视网膜组织结构无明显异常改变。 结论 纤溶酶联合透明质酸酶或SF6较单独采用纤溶酶更能迅速有效的诱发完全性PVD且对视网膜无明显的毒性作用。 (中华眼底病杂志, 2005, 21: 388-390)     

Evaluation of <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> staphylolysin (LasA protease) in the treatment of methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> endophthalmitis in a rat model

Background  Therapy of S. aureus ocular infections is increasingly challenging due to emerging resistant strains. Staphylolysin (also called LasA protease) is a staphylolytic endopeptidase secreted by Pseudomonas aeruginosa. The purpose of this study was to evaluate the efficacy of staphylolysin as a therapy for experimental methicillin-resistant Staphylococcus aureus (MRSA) endophthalmitis, focusing on its bactericidal activity. Methods  Endophthalmitis was induced in the right eyes of 46 rats by an intravitreal injection of 50–160 MRSA cells. Two therapeutic regimens were evaluated: (i) an intravitreal injection of staphylolysin at 6 hours post-infection; (ii) two successive intravitreal injections of staphylolysin given at 6 and 30 hours post-infection. Control eyes were injected with vehicle alone at the same times. The rats were sacrificed 48 hours after infection, and the vitreous was withdrawn for determination of colony forming units (CFU). Potential adverse effects of intravitreal staphylolysin injection were assessed histopathologically in four uninfected eyes, enucleated from rats sacrificed 1 month after intravitreal staphylolysin injection. Results  In eyes treated by the single-injection regimen, staphylolysin reduced the mean CFU value per vitreous threefold as compared to control (2,055 ± 3,144 and 6,432 ± 6,389 CFU/vitreous, respectively; P = 0.02). The repeated injection protocol was more effective, reducing the mean CFU value per vitreous by two orders of magnitude as compared to control (1,148 ± 3,096 and 143,519 ± 151,358 CFU/vitreous, respectively; P = 0.0005). Histopathological analysis showed no structural damage in eyes injected intravitreally with staphylolysin. Conclusions  Staphylolysin is effective in the treatment of experimental MRSA-induced endophthalmitis in rats, and causes no morphological adverse effects to ocular tissues. Staphylolysin may be beneficial in the treatment of S. aureus endophthalmitis in humans. The authors have no proprietary interest in any aspect of this study. The authors have full control of all primary data, and they agree to allow Graefe's Archive for Clinical and Experimental Ophthalmology to review their data upon request.     

Preclinical investigation of fluorometholone acetate as a potential new adjuvant during vitreous surgery

Objective To examine the effects of intravitreal fluorometholone acetate (FMT) on the morphology and function of the retina and to investigate its possible use for vitreous surgery. Methods Brown Norway rat eyes (n = 6, 12 groups) were injected with 0.05 ml of SF₆ gas for vitrectomization. Four weeks later, FMT solution was injected into the vitreous cavity/subretinal space of the vitrectomized eyes at doses of 10, 20, and 40 mg/ml (0.05 ml/eye, n = 12 for each group). The retinal function was evaluated by electroretinography (ERG) at 4 and 8 weeks after FMT injection. Retinal toxicity was also assessed histologically by a light microscopy. Sham-operated eyes (0.05 ml of irrigating solution, n = 12) were used as control animals. FMT-assisted pars plana vitrectomy with internal limiting membrane (ILM) peeling was performed in primate eyes (n = 2). Retinal toxicity was assessed by ophthalmoscope, fluorescein angiography and electron microscopy three months after the vitreous surgery. Results There was no remarkable reduction in any ERG waves at either time interval at 4 and 8 weeks after the intravitreal/subretinal injection of FMT. No obvious histological change was observed in any of the rat eyes either. Using ophthalmoscope, fluorescein angiography and electron microscopy, the appearance of the primate retinas remained to be in a non-pathological condition. Conclusion FMT appears to be a potentially useful tool in assisting vitreous surgery including safe ILM peeling. The study was supported in part by grants from the Ministry of Education, Science, Sports and Culture, Japan (Grant-in-Aid for Scientific Research #17591839, #14571676).     

Intravitreal bevacizumab for refractory choroidal neovascularization (CNV) secondary to uveitis

Purpose  To assess the short-term efficacy and safety of intravitreal bevacizumab injections (IVB) for refractory choroidal neovascularization (CNV) secondary to uveitis. Methods  Ten patients affected by choroidal neovascularization secondary to uveitis unresponsive to immunosuppression associated or not with photodynamic therapy (PDT) were consecutively included. All patients underwent a complete ophthalmic examination including best-corrected visual acuity (BCVA), fluorescein (FA) and indocyanine green angiographies (ICG), optical coherence tomography (OCT) at baseline, and after IVB injection (1.25 mg/0.05 ml). Results  CNV was subfoveal in eight cases and juxtafoveal in two cases. Mean follow-up was 7.5 months. After treatment, the logMAR BCVA improved from 0.62 ± 0.4 (Snellen equivalent of 20/55) to 0.45 ± 0.35 (Snellen equivalent of 20/40) at 1 month (p = 0.01), then remained stable during the follow-up. Mean central macular thickness (CMT) was reduced from 326 ± 95 μm before treatment to 267 ± 28 μm (p = 0.03) at last visit. Mean number of IVB was 2.5. Leakage from inflammatory CNV was stopped in three eyes and decreased in seven eyes. No systemic or ocular adverse events were recorded. Conclusions  Intravitreal bevacizumab improves BCVA and reduces central macular thickness in eyes with inflammatory CNV refractory to immunosuppression associated or not with PDT. Further study is necessary to assess the efficacy and safety in the long term. None of the authors has any financial interest in this study. The authors have full control of all primary data and agree to allow Graefe’s Archive for Clinical and Experimental Opthalmology to review the data if requested.     

纤溶酶和透明质酸酶诱导猪玻璃体后脱离的实验研究

目的研究纤溶酶和透明质酸酶诱导猪玻璃体后脱离(PVD)的有效性和安全性,比较两种酶单独应用和联合应用的效果。方法15只小型猪随机分为A、B、C三组,每组5只,随机选取一只眼为实验眼,对侧眼为对照眼,A组实验眼玻璃体腔注射50U/0.1ml透明质酸酶,B组实验眼注射0.5U/0.1ml纤溶酶,C组实验眼注射0.5U/0.05ml纤溶酶和50U/0.05ml透明质酸酶,对照眼均注射平衡盐溶液(BSS)0.1ml。注药后进行裂隙灯、直、间接检眼镜、眼B超、视网膜电图(ERG)等检查,7d后摘除眼球进行光镜、透射电镜、扫描电镜检查。结果B超检查显示A组有一只实验眼、B组有两只实验眼于注药后1d观察到部分性PVD,C组有一只实验眼于注药后1h观察到部分性PVD。B超、光镜和扫描电镜检查显示注药后7dA组和B组实验眼均见部分性PVD,C组实验眼均见完全性PVD,对照眼未见PVD。实验及对照眼注药前、后ERGa波、b波波幅均无显著性差异,光镜及透射电镜检查未见视网膜损害。结论0.5U纤溶酶和50U透明质酸酶单独及联合应用均可快速、安全、有效地诱导猪眼玻璃体后脱离,且联合用药较单独用药诱导PVD更快速、更有效。     

Retinal toxicity of triamcinolone’s vehicle (benzyl alcohol): an electrophysiologic and electron microscopic study

Purpose To assess retinal toxicity of the vehicle of triamcinolone, benzyl alcohol (BA), when injected into the vitreous cavity of rabbits. Methods This prospective comparative experimental study included 24 pigmented rabbits assigned into two groups: group 1 (experimental, n = 12) received intravitreal 0.1 ml of BA, and group 2 (control, n = 12) received intravitreal 0.1 ml of balanced salt solution (BSS); all injections were done in the right eyes. Clinical examinations [slit lamp biomicroscopy, indirect ophthalmoloscopy, and three intraocular pressure (IOP) measurements] were done on both eyes before injection, at 1 and 3 h post injection, together with electroretinograms (ERGs) at 3 days, 1, 2, 4, and 6 weeks following injections. Three rabbits from each group were euthanased at 1, 2, 4, or 6 weeks and eyes were sent for light and electron microscopic examination for quantitative morphometric measurements. Results The mean amplitudes of the a and b waves of the BA-injected eyes were 6.42 ± 9.02 μv and 11.18 ± 15.18 μv at 3 days, respectively, which were significantly reduced compared with the BSS-injected eyes (30.87 ± 8.22 μv and 57.90 ± 13.38 μv, respectively; P < 0.01 t-test) and the non-injected contralateral eyes (36.20 ± 7.85 μv and 64.10 ± 9.36 μv, respectively; P < 0.01 t-test). These ERG responses continued to be significantly reduced in the BA-injected eyes (P < 0.01 t-test) throughout the study period. The mean ganglion cell count was significantly reduced (P < 0.005 t-test) in the BA-injected eyes (8.42 ± 2.4) compared with the BSS- and non-injected eyes (16.42 ± 3.9 and 16.5 ± 4.2, respectively). The mean thicknesses of the inner nuclear layer (INL) and outer nuclear layer (ONL) were significantly reduced (P < 0.005 t-test) in the BA-injected eyes (3.78 ± 0.96 μm and 11.77 ± 1.29 μm, respectively) compared with the BSS- (6.1 ± 0.92 μm and 21.82 ± 0.95 μm, respectively) and non-injected eyes (7.05 ± 1.9 μm and 22.49 ± 1.01 μm, respectively). Electron microscopy showed moderate to severe intracellular changes in the ganglion cell layer, INL, ONL, and photoreceptor layer at 6 weeks in BA-injected eyes, with no significant changes in BSS-injected eye. There was no significant rise in the IOP or clinical evidence of increased lens density during the study period in any of the eyes. Conclusions Triamcinolone acetonide’s vehicle, BA, produced severe ERG and structural damage to the retina when injected intravitreally.     

Efficacy and safety of latanoprost in eyes with uveitic glaucoma

Background  To compare the efficacy and safety of latanoprost against a fixed combination of dorzolamide and timolol in eyes with elevated intraocular pressure (IOP) or glaucoma and anterior or intermediate uveitis. Methods  Fifty-eight patients with anterior or intermediate uveitis and elevated IOP or glaucoma presented or followed up in the Ocular Inflammation and Immunology Service of General Hospital of Athens were randomly assigned to receive treatment either with latanoprost (30) or with dorzolamide/timolol (28). The main outcome measures were inflammatory relapses and IOP response to treatment. Results  Ten patients (34%) in the latanoprost group and sixteen patients (57%) in the dorzolamide/timolol group experienced relapses of anterior uveitis (p = 0.93). There was no statistical difference between the two groups in respect of inflammatory relapses (p = 0.21). Twenty-one patients were followed up before starting latanoprost. The number of recurrences of anterior uveitis per patient per year before treatment with latanoprost was 0.82 ± 1.2. The rate of relapses per patient per year after starting latanoprost was 0.39 ±0.7 for these patients (p = 0.038). After 1 year of treatment, intraocular pressure was dropped from 27.8 ± 8.4 mmHg to 18.6 ± 5.3 mmHg (p < 0.001) in the latanoprost group and from 28.2 ±8.1 mmHg to 22.6 ±10.1 mmHg (p < 0.001) in the dorzolamide/timolol group. Four patients during treatment with latanoprost and five patients during treatment with dorzolamide/timolol developed macular edema. Conclusion  Latanoprost is safe and equally effective to a fixed combination of dorzolamide and timolol in the treatment of uveitic glaucoma. The authors have no proprietary interest in any aspect of this study.     

Effect of vitrectomy on macular microcirculation in patients with diffuse diabetic macular edema

Purpose  To determine whether retinal microcirculatory changes occur after vitrectomy in eyes with diffuse diabetic macular edema (DME), and whether changes in blood flow are associated with visual outcome and the resolution of macular edema. Methods  Thirty-three eyes of 30 consecutive diabetic patients who underwent pars plana vitrectomy for diffuse DME, and 16 eyes of 16 diabetic patients without macular edema, were included. Mean macular blood flows were measured using a Heidelberg Retinal Flowmeter, and central macular thicknesses (CMTs) were determined by optical coherence tomography. Visual outcomes, CMTs, and macular blood flow were evaluated before and 1, 4, 12 weeks after vitrectomy, and compared between eyes with resolved macular edema and those with persistent macular edema. Results  Mean preoperative macular blood flow in eyes with diffuse DME was higher than in controls (606.5±357.9 AU vs 407.1±265.9 AU, P=0.021). Mean macular blood flow (422.6±247.5 AU) at 12 weeks after vitrectomy was significantly lower than preoperative blood flow (P=0.002), and similar to that of controls (P=0.47). In 22 of the 33 (66.7%) DME eyes, macular edema was resolved at 12 weeks after vitrectomy. The mean ratio of macular blood flow at 12 weeks postoperatively versus the preoperative level was significantly lower in eyes with resolved macular edema than in eyes with persistent macular edema (0.65 vs 1.08, P<0.001). Conclusions  Increased macular blood flow in diabetic macular edema was normalized after vitrectomy in eyes with resolved macular edema. Changes of macular blood flow may be associated with the resolution of macular edema in diabetic eyes. This study was supported by a grant from the Korea Healthcare Technology R&D Project (A080588), Ministry of Health & Welfare, Republic of Korea.     

Ophthalmodynamometry and ischemic ophthalmopathy

Background To report on the clinical application of a modified ophthalmodynamometer for the detection of ischemic ophthalmopathy. Methods A 70-year-old patient showed unilateral loss of vision to 1/20, thin retinal arteries, tiny intraretinal hemorrhages, and iris neovascularization. We performed a modified ophthalmodynamometry using a Goldmann contact lens in the holding grip of which a pressure sensor was incorporated. Results Ophthalmodynamometry showed that the diastolic central retinal artery pressure was significantly (p < 0.001) lower in the affected eye than in the contralateral eye (14.6 ± 2.2 arbitrary units versus 45.5 ± 5.1 arbitrary units). These ophthalmodynamometric measurements of both eyes were significantly (p < 0.05) lower than in a control group (73.8  ± 6.2 arbitrary units) consisting of 149 normal eyes. Doppler sonography eventually revealed a marked stenosis of the right internal carotid artery, consistent with the diagnosis of a unilateral ischemic ophthalmopathy. Conclusions Ophthalmodynamometry is a helpful additional tool in the assessment of the oculo-afferent and cerebroafferent vessels in patients with symptomatic ocular ischemia.     

Minimally invasive strabismus surgery (MISS) for inferior obliquus recession

Purpose  To present a novel, minimally invasive strabismus surgery (MISS) technique for inferior obliquus recessions. Methods  Graded MISS inferior obliquus recessions were performed in 20 eyes of 15 patients by applying two small conjunctival cuts, one at the insertion of inferior obliquus and another where the scleral anchoring of the muscle occurred. Results  The amount of recession was 12.2 ± 2.3 mm (range 6 to 14 mm). The vertical deviation, which was measured in 25° of adduction, decreased from preoperatively 12.8° ± 5.6° to 2.7° ± 2.2° (p < 0.0001) at 6 months. LogMAR visual acuity was preoperatively −0.10 ± 0.17 and at 6 months −0.14 ± 0.22 (p > 0.1). In one eye (2.5%) the two cuts had to be joined because of excessive bleeding. Binocular vision improved in eight patients, remained unchanged in six patients, and decreased from 30 to 60 arcsec in one patient (p > 0.1). Conjunctival and lid swelling were hardly visible on the first postoperative day in primary gaze position in 10/20 (50%) of eyes. Five of the eyes (25%) had mild and five (25%) moderate visibility of surgery. One patient out of 15 (7%) needed repeat surgery because of insufficient reduction of the sursoadduction within the first 6 months. The dose–effect relationship 6 months postoperatively for an accommodative near target at 25° adduction was 0.83° ± 0.43° per mm of recession. Conclusions  This study demonstrates that small-incision, minimal dissection inferior obliquus graded recessions are feasible and effective to improve ocular alignment in patients with strabismus sursoadductorius. Approval: This research followed the tenets of the Declaration of Helsinki. The president of the Ethical Committee of Kanton St. Gallen has approved the use of this new technique. The author has no financial interests in the new technique.     

Assessment of selected adhesion molecule and proinflammatory cytokine levels in the vitreous body of patients with type 2 diabetes — role of the inflammatory–immune process in the pathogenesis of proliferative diabetic retinopathy

Background  The aim of the study is to demonstrate the participation of the inflammatory-immune process in the pathogenesis of proliferative diabetic retinopathy (PDR). Methods  Twenty four women and 22 men with type 2 diabetes (mean age 63.97 ± 9.00 years, mean duration of diabetes 12.56 ± 6.87 years) were enrolled in the study. Serum concentrations of soluble forms of ICAM-1, VCAM-1 as well as IL-6 and TNF-α were evaluated in all study subjects. In 19 patients, simultaneous assessment of selected parameter levels in both serum and vitreous samples was performed. Vitrectomy was performed due to intravitreal hemorrhage, accompanied in some patients by traction retinal detachment. The control group consisted of 15 patients having undergone vitrectomy for reasons other than PDR. Tests were performed using the ELISA method. Results  Serum and intraocular concentrations of sICAM-1, sVCAM-1, IL-6, TNF-α were considerably higher in study subjects with PDR than in controls. Simultaneously, a positive correlation was found between intraocular sVCAM-1 (r = 0.590, p = 0.007), TNF-α (r = 0.822, p < 0.001) concentrations and HbA₁c levels. The above-mentioned dependence was not shown for sICAM-1 and IL-6 vitreous concentration. Local vitreous VCAM-1 level increase was also dependent on vitreous TNF-α concentration growth (r = 0.470, p = 0.043). No significant correlation was found between serum and vitreous levels of the selected parameters in the group of 19 patients with PDR. Conclusions  Increase in sICAM-1 and sVCAM-1 levels, as well as their correlation with high vitreous IL-6 and TNF-α concentrations in patients with PDR, seem to confirm the inflammatory–immune nature of this process. In diabetes, inadequate metabolic control remains an important risk factor in the development of PDR. We disclose commercial or similar relationships to products or companies mentioned in or related to the subject matter of the article being submitted. We have full control of all primary data and we agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review our data if requested.     

Preservation of photoreceptors in dystrophic RCS rats following allo- and xenotransplantation of IPE cells

Purpose  To examine whether iris pigment epithelial (IPE) cells transplanted into the subretinal space of Royal College of Surgeons (RCS) rats have the ability to rescue photoreceptors. Methods  Rat IPE (rIPE) or human IPE (hIPE) cells were transplanted subretinally in 23-day-old RCS rats. Sham injection and transplantation of ARPE-19 cells served as controls. After 12 weeks, eyes were evaluated for photoreceptor survival by morphometric analysis and electron microscopy. Results  Morphometric analysis showed photoreceptor rescue in all transplanted and sham-injected animals (number of photoreceptors/300 μm retina±sd: rIPE 41.67 ± 28; hIPE 29.50 ± 16; ARPE-19 36.12 ± 21; sham 16.56 ± 6) compared to age-matched, control rats (number of photoreceptors/300 μm retina±sd: 9.71 ± 4). Photoreceptor rescue was prominent in IPE cell-transplanted rats and was significantly greater than sham-injected eyes (p = 0.02 for rIPE and p = 0.04 for hIPE). Conclusion  Since IPE cells transplanted into the subretinal space have the ability to rescue photoreceptors from degeneration in the RCS rat without any harmful effects, IPE cells may represent an ideal cell to genetically modify and thus carry essential genetic information for the repair of defects in the subretinal space.