The capillary blood flow in ischaemic type central retinal vein occlusion: the effect of laser photocoagulation

PURPOSE: To determine the effect of photocoagulation on retinal blood flow (RBF) in eyes with ischaemic type central retinal vein occlusion (CRVO). PATIENTS AND METHODS: Retinal blood flow was measured in 12 eyes with CRVO, 12 fellow eyes and 12 eyes of 12 age-matched healthy subjects using the Heidelberg retinal flowmeter (HRF). Microvascular blood flow values (volume, flow, velocity) were recorded from the upper temporal retina and macula. Eyes were re-examined 1 month after photocoagulation. We investigated whether there was a difference in RBF measurements before and after photocoagulation treatment. RESULTS: In eyes with CRVO, mean RBF values (volume, flow and velocity) obtained from the upper temporal retina increased significantly after treatment (paired t-test, p < 0.05). In contrast, mean RBF values from the macula were unaffected by photocoagulation (paired t-test, p > 0.05). Retinal blood flow values from the upper temporal retina obtained from control subjects were significantly higher than the values in eyes with CRVO before and after photocoagulation (unpaired t-test, p < 0.05), but there was no significant difference between control subjects and CRVO patients in RBF values from the macula (unpaired t-test, p > 0.05). Mean RBF values were significantly higher in CRVO patients' fellow-eyes before photocoagulation in the eyes with CRVO (paired t-test, p < 0.05) but were lower than in age-matched healthy control eyes (unpaired t-test, p < 0.05). Macular blood flow did not differ between the eyes with CRVO and fellow eyes (paired t-test, p > 0.05). CONCLUSION: Laser photocoagulation increased retinal blood flow in eyes with CRVO, but RBF did not reach normal values. Photocoagulation was found to have no effect on RBF in the macular area.     

Evaluation of potential retinal toxicity of adalimumab (Humira)

Purpose  The purpose of this study is to evaluate the retinal toxicity of two doses of adalimumab (Humira), a recombinant human IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF), when injected intravitreally in rabbits. Methods  Sixteen male pigmented rabbits (divided into two groups, eight animals per group) were used for this study. Two concentrations of adalimumab were tested: 0.5 mg/0.1 ml and 5 mg/0.1 ml. Each concentration was injected intravitreally randomly in one eye (study group) of each rabbit (group I received 0.5 mg/0.1 ml and group II received 5.0 mg/0.1 ml), while in the other eye (control group) 0.1 ml of sterile balanced saline solution (BSS) was injected. Slit-lamp and funduscopic examinations were performed every second day for 2 weeks for signs of infection, inflammation and toxicity. A baseline electroretinogram (ERG) was performed before the experiment and at the last follow-up day (day 14). ERG examination followed ISCEV standards. At the last follow-up day, the animals were sacrificed and the enucleated eyes were prepared for histological evaluation of retinal toxicity. Results  No differences in ERG responses at photopic and scotopic conditions were observed in eyes injected with either concentration of adalimumab or BSS. Furthermore, histologic examination of the retina in the enucleated eyes (in all groups) did not demonstrate any evidence of drug toxicity. Conclusions  Intravitreal adalimumab did not appear toxic to the retina in this experimental model at concentrations of 0.5 and 5 mg. If found safe in additional studies, intravitreally injected adalimumab could be evaluated for efficacy in the treatment of inflammatory eye conditions.     

Treatment of recent onset central retinal vein occlusion with intravitreal tissue plasminogen activator: a pilot study

AIMS: To study the effects of intravitreal tissue plasminogen activator (tPA) in recent onset central retinal vein occlusion (CRVO). METHODS: 15 patients with recent onset CRVO (from 1-21 days' duration, mean 8 days) were given 75-100 microg of tPA intravitreally associate with low dose low molecular weight heparin. CRVO was perfused in nine patients and with mild ischaemia not exceeding 100 disc diameters in six patients. Follow up ranged from 5 to 21 months for 14 patients (mean 8 months). Visual acuity measurement, macular threshold (Humphrey perimeter), fluorescein angiography with the scanning laser ophthalmoscope with special emphasis on retinal circulation times, and retinal perfusion were performed at days 0, 1, and 8 and months 1, 3, and 6. RESULTS: Visual acuity was significantly improved on the first day after treatment in only one eye, and decreased transiently in six eyes (40%). Retinal blood velocity was not significantly modified by tPA injection. Retinal ischaemia developed in six eyes (43%), leading to panretinal photocoagulation in five eyes including one with rubeosis iridis. At the end of follow up, visual acuity had improved to 20/30 or better in five eyes (36%), including two with complete recovery; visual acuity was worse than 20/200 in three eyes (28%). No complication of tPA injection was observed. CONCLUSION: Intravitreal tPA treatment for CRVO appears to be simple and safe, but did not significantly modify the course of the occlusion in our patients immediately after treatment. Final visual outcome did not differ significantly from that observed in the natural course of the disease, but final visual acuity seemed to be slightly better. A randomised study is required to determine if intravitreal tPA actually improves visual outcome in CRVO.     

A moephologic study of retinal toxicity induced by triamcinolone acetonide vehicles in rabbit eyes

PURPOSE: To evaluate the toxic effects of two triamcinolone acetonide (TA) vehicles on rabbit retina at different volumes. METHODS: Vehicle A and B were prepared from two TA injections by centrifugation. Thirty-six New Zealand white rabbits were intravitreally injected with vehicle A, B, or balanced saline solution at 0.1 mL or 0.2 mL respectively. The eyes were examined by indirect ophthalmoscope, light microscope, and transmission electron microscope up to week 8 postinjection. RESULTS: Eyes with vehicle A appeared normal under the ophthalmoscope, but showed disorganization in retinal inner nuclear layer and photoreceptor layer in pathologic analyses. Eyes with vehicle B displayed more significant retinal changes including retinal hemorrhage, vascular narrowing, myelinated fiber edema, retinal necrosis and atrophy, and photoreceptor apoptosis. There was an increase in degree of the above damages as the volume of either vehicle increased. CONCLUSION: Both vehicle A and B caused volume-related toxicity in rabbit retina. The intensity of the toxic effects of different vehicles may differ. Reducing or decanting the vehicles should be considered before intravitreal use of TA injections.     

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.     

Absence of histologic retinal toxicity of intravitreal bevacizumab in a rabbit model

PURPOSE: To evaluate the retinal toxicity of intravitreal bevacizumab in an animal model. DESIGN: Animal study. METHODS: Bevacizumab was injected into the vitreous of one eye of each of eight Dutch-belted rabbits; the other eye served as a control. Four rabbits received a dose of 1.25 mg/0.05 ml of bevacizumab intravitreally into one eye, and the other four rabbits were injected with 2.5 mg/0.1 ml of bevacizumab intravitreally into one eye. At one month, the rabbits were killed and both eyes enucleated. The eyes were fixed with paraformaldehyde 2% and examined by light microscopy. RESULTS: In all injected and control eyes, there was mild vacuolization in the ganglion cell layer, and disruption of photoreceptor outer segments in both treated and control eyes, to the same degree, consistent with autolysis. The optic nerve, retina, and retinal pigment epithelium were otherwise normal by light microscopy with no evidence of toxicity. CONCLUSIONS: Intravitreal bevacizumab at doses of 1.25 mg and 2.5 mg showed no signs of retinal or optic nerve toxicity by light microscopy in this rabbit model.     

Absence of histologic retinal toxicity of intravitreal nanogold in a rabbit model

PURPOSE: To evaluate the retinal toxicity of intravitreal nanogold, a novel antiangiogenic and long-term delivery agent. METHODS: One eye of each of 16 Dutch-belted rabbits was injected with intravitreal nanogold; the other eye served as a control. Eight rabbits received a dose of 67 micromol/0.1 mL of nanogold intravitreally into 1 eye; the other 8 rabbits received a dose of 670 micromol/0.1 mL of nanogold intravitreally into 1 eye. Eight rabbits were killed at 1 week, and eight were killed at 1 month; both eyes of each rabbit were enucleated. The eyes were fixed with 2% paraformaldehyde and sectioned for histologic examination. RESULTS: In all injected and control eyes, there was mild vacuolization in the inner plexiform and ganglion cell layers. The retina and retinal pigment epithelium were otherwise histologically normal. CONCLUSION: Intravitreal nanogold at concentrations of 67 micromol/0.1 mL and 670 micromol/0.1 mL showed no signs of retinal or optic nerve toxicity by light microscopy during histologic examination at 1 month.     

纤维蛋白溶解酶和Dispase蛋白酶诱导兔眼玻璃体后脱离的实验研究

目的研究纤维蛋白溶解酶和dispase蛋白酶诱导玻璃体后脱离(PVD)的作用。方法24只健康成年的青紫兰兔随机分为4组,右眼均为实验眼,左眼为对照眼。A组实验眼玻璃体腔内注射纤溶酶1U,B组纤溶酶2 U,C组dispase蛋白酶0.0125U和D组dispase蛋白酶0.025U,对照眼均为眼用平衡盐BSS液0.1 ml。注药前后行眼底镜、裂隙灯和VOLK 90D前置镜以及B超和视网膜电图(ERG)检查,最后取眼球进行光镜、扫描电镜和透射电镜观察。结果电镜结果A组2只实验眼后极部发生不完全性PVD,发生率为33.3%;B、C两组实验眼中各有4只眼发生完全性PVD。发生率为66.7%;D组实验眼有5只眼发生完全性PVD,发生率为83.3%。纤溶酶各组实验眼注药后ERG振幅与术前及对照眼比较无显著性差异(P>0.05),光镜和透射电镜观察视网膜组织结构正常,均未发现明显异常改变。而Dispase蛋白酶各组透射电镜观察视网膜细胞和细胞器出现水肿和变性。ERG检测Dispase两组实验眼术后b波振幅较术前明显降低(P<0.01)。结论玻璃体腔注射纤溶酶2U较注射1U更能有效的诱导PVD且对视网膜无明显的毒性作用。而Dispase蛋白酶虽然可迅速有效的诱导PVD,但对视网膜有明显的毒性作用。     

The neuropeptide NAP provides neuroprotection against retinal ganglion cell damage after retinal ischemia and optic nerve crush

Background  NAP, an 8-amino acid peptide (NAPVSIPQ=Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln) derived from activity-dependent neuroprotective protein (ADNP), plays an important role in neuronal differentiation and the survival of neurons in different pathological situations. We already discovered that NAP increases the survival of retinal ganglion cells (RGC) in vitro, and supports neurite outgrowth in retinal explants at femtomolar concentrations. The aim of this study was to investigate the effects of NAP on RGC survival after transient retinal ischemia and optic nerve crush. Methods  RGC of male Wistar rats were labelled retrogradely with 6 l FluoroGold injected stereotactically into both superior colliculi. Seven days later, retinal ischemia was induced by elevating the intraocular pressure to 120 mm Hg for 60 minutes or by crushing one optic nerve for 10 s after a partial orbitotomy. NAP was either injected intraperitoneally in the concentration of 100 mg/kg 1 day before, directly after, and on the first and the second days after damage, or intravitreally (0.05 or 0.5 μg/eye) directly after the optic nerve crush. Controls received the same concentrations of a control peptide. Densities of surviving RGC and activated microglial cells (AMC) were quantified in a masked fashion 10 days after damage by counting FluoroGold-labelled cells. Results  After retinal ischemia, intraperitoneal injections of NAP increased the number of surviving RGC by 40% (p < 0.005) compared to the control group. After optic nerve crush, NAP raised the number of surviving RGC by 31% (p = 0.07) when injected intraperitoneally and by 54% (p < 0.05) when administered intravitreally. Conclusions  NAP acts neuroprotectively in vivo after retinal ischemia and optic nerve crush, and may have potential in treating optic nerve diseases. Supported by the Ernst und Berta Grimmke Stiftung, Germany. IG is the incumbent of the Lily and Avraham Gildor Chair for the Investigation of Growth Factors and the Director of the Adams Super Center for Brain Research at Tel Aviv University and is the Chief Scientific Officer of Allon Therapeutics Inc., Vancouver, Canada. An erratum to this article can be found at     

Transferrin–Ricin A Chain Toxin Limits the Development of Experimental Proliferative Vitreoretinopathy

This study was designed to determine the safety and efficacy of transferrin–ricin A chain toxin (Tfr-rRA) at preventing retinal detachment in a rabbit model of proliferative vitreoretinopathy (PVR). The toxicity of intravitreal Tfr-rRA (1000–5000ng) was determined by indirect ophthalmoscopy and electroretinography on days 1, 5, 8, 16, 26 and 48 post-injection, and by light and transmission electron microscopy conducted on eyes enucleated 48 days after drug exposure. PVR was created by injecting 25000 homologous fibroblasts into the vitreous cavity of eyes which had previously undergone a gas compression vitrectomy. Eyes then received intravitreal Tfr-rRA (2000ng) or vehicle. Animals were examined on days 1, 4, 7, 10, 14, 21 and 28 post-injection. Intravitreal injection of 1000 and 2000ng Tfr-rRA did not show ophthalmoscopic or electroretinographic toxicity. Injection of 5000ng Tfr-rRA showed mild retinal whitening, retinal arteriolar narrowing, and electroretinographic toxicity, but no morphologic damage, such as photoreceptor loss, nuclear layer vacuolation, or inflammatory cell infiltration, to the retina. Tfr-rRA (2000ng) injected intravitreally 3 days after fibroblast injection prevented traction retinal detachment in 90% of eyes compared to 22% of sham treated eyes (P< 0.001). The data from this study suggest that transferrin-ricin A chain toxin (2000ng) safely and effectively limits retinal detachment in experimental PVR.     

Retinal toxicity of liposome-incorporated and free ofloxacin after intravitreal injection in rabbit eyes

Background: Ofloxacin (OFLX) is a fluoroquinolone-antibiotic with a broad antimicrobial spectrum that may have a potential role in the treatment of bacterial endophthalmitis. However, its elimination half life after intravitreal injection is short. To prolong the intravitreal antibacterial level OFLX was incorporated into liposomes. This study was performed to investigate the retinal toxicity of liposome-incorporated and free OFLX. Materials and methods: OFLX was incorporated into multilamellar large vesicles. 0,1 ml of this suspension (= 180.2 μg OFLX) was injected into the midvitreous of rabbit eyes (n = 6). Free OFLX in doses of 100 μg, 500 μg and 1,000 μg was injected into the midvitreous of a second group of rabbit eyes (n = 18). The other eye served as a control and received empty liposomes or normal saline solution, respectively. Before injection and at the end of follow-up an ERG was obtained. After a follow-up of 1 day, 14 and 28 days the animals were perfused with glutaraldehyde and the eyes were examined by light- and transmission electron microscopy. Results: The ERG as well as the histologic studies did not reveal any pathological changes after injection of liposome-incorporated OFLX compared to the control eyes. Significant reduction of the ERG was observed after 500 μg free OFLX in 2 out of 6 eyes after 1 and 14 days, respectively, and in 2 eyes 1 day after 1,000 μg free OFLX. Three days after injection of 1,000 μg OFLX the retina showed focal destruction in 1 out of 6 eyes. In another eye with the same dose 14 days after injection the photoreceptor outer segments showed disorganisation. Conclusion: This study shows that liposome-incorporated OFLX did not have any retinal toxicity in this animal model. Free OFLX appears to have no retinal toxicity in rabbit eyes at a dose of 100 μg after intravitreal injection. Injection of higher doses resulted in ERG changes and marked retinal damage. This revised version was published online in July 2006 with corrections to the Cover Date.     

Use of Perfluorocarbon Liquids, Silicone Oil, and 5-Fluorouracil in the Management of Experimental PVR

Purpose: To evaluate the toxicity and efficacy of 5-fluorouracil (5-FU) in combination with perfluoroperhydrophenanthrene (Vitreon), silicone oil, or a combination of silicone oil and Vitreon in a ratio of 3:2 in the management of experimental proliferative vitreoretinopathy (PVR). Methods: Toxicity study. Seventy rabbit eyes underwent vitrectomy followed by intravitreal injection of 5-FU in doses of 800, 400, or 200 μg: Group 1, 5-FU alone; Group 2, 5-FU plus 1 mL Vitreon; Group 3, 5-FU plus 1 mL silicone oil; Group 4, 5-FU plus 0.6 mL silicone oil and 0.4 mL Vitreon; Group 5, 0.6 mL silicone oil plus 0.4 mL Vitreon. Electroretinography was performed preoperatively and 8 weeks postoperatively before the animals were sacrificed. Efficacy study. Seventy-two rabbit eyes underwent vitrectomy and were injected intravitreally with 100,000–200,000 retinal pigment epithelial cells to induce PVR. Groups were injected with 200 μg 5-FU alone or with 1 mL silicone oil, 1 mL Vitreon, or a combination of 0.6 mL silicone oil and 0.4 mL Vitreon. Others were given only 1 mL Vitreon or 1 mL silicone oil. The animals were followed for 8–12 weeks; PVR was graded using Fastenberg's system. Results: Toxicity study. Eyes given 200 μg 5-FU, silicone, and Vitreon showed mild inflammation and vitritis which resolved in 1 week; the dose was nontoxic by electroretinography and histopathology. Doses of 400 and 800 μg 5-FU were toxic. Efficacy study. Clinical severity of PVR was less in the groups which received 5-FU plus vitreous substitutes when compared to the control groups at all time points. The lowest incidences were in groups given 5-FU plus Vitreon or 5-FU plus Vitreon and silicone oil: 33.33% and 11.11%, respectively. Conclusions: A dose of 200 μg 5-FU with silicone oil and Vitreon combined was nontoxic to the rabbit retina. The combination of 5-FU, Vitreon, and silicone oil showed significant efficacy in the prevention of experimental PVR. This revised version was published online in July 2006 with corrections to the Cover Date.     

Effect of VEGF trap on normal retinal vascular development and oxygen-induced retinopathy in the dog

Purpose. To evaluate the effects of a vascular endothelial growth factor trap (VEGF Trap) on retinal vascular development and pathologic neovascularization (NV) in the canine model of oxygen-induced retinopathy (OIR). Methods. Newborn dogs (postnatal day [P]1) were exposed to 100% O(2) and then returned to room air on P5. VEGF Trap (5, 25, or 250 μg) was injected intravitreally in one eye and human FC (hFc) injected in the fellow eye of air control and oxygen-treated dogs on P8. The retinal vasculature and NV were evaluated on P21. Other oxygen-exposed animals received 5 μg of VEGF Trap or hFc on P22 after confirmation of retinopathy of prematurity (ROP)-like pathology and were evaluated at P45. Results. In air controls, both the vascularized area of the retina and the density of superficial capillaries were reduced in 250 or 25 μg VEGF Trap-injected eyes, and deep capillaries were absent. Eyes that received the 5 μg dose were indistinguishable from controls. In oxygen-treated animals, all eyes injected with VEGF Trap exhibited markedly less intravitreal NV than that of hFc-injected fellow eyes, irrespective of dose. Retinal vascular area in OIR animals was significantly reduced in eyes injected with 250 or 25 μg of VEGF Trap, but the 5 μg dose did not inhibit retinal revascularization. Eyes with existing NV that received 5 μg VEGF Trap at P22 exhibited substantial resolution of OIR pathology at P45. Conclusions. The VEGF Trap inhibited the formation of NV, but higher doses also inhibited revascularization of retina when injected at P8. In contrast, the lowest dose tested effectively blocked NV and caused regression of existing NV, without appreciably affecting vasculogenesis or retinal revascularization. These findings suggest that dose selection is an important variable when considering the use of VEGF-targeting agents for the treatment of ROP.     

Ameliorative effect of PN-277 on laser-induced retinal damage

Background  The retinal damage induced by laser photocoagulation increases considerably by the secondary degeneration process whereby tissues adjacent to the primary lesion are destroyed. As the neuroprotective effect of immunization by PN-277 was previously demonstrated in models of retina, optic nerve, brain, and spinal cord lesions, it may be used also for reducing retinal damage induced by laser. The aim of this study was to evaluate the neuroprotective effect of immunization with PN-277 in reducing the spread of laser-induced retinal damage. Methods  Standard argon laser lesions were created in 36 DA pigmented rats. Seven days before exposure to laser, the rats were divided into a test group (n = 18) that was pre-immunized with intraperitoneal injection of PN-277 and control group (n = 18) treated with saline. Histological and morphometrical evaluations of the retinal lesions were preformed 3, 20, and 60 days after the injury. Results  Significant ameliorative effect was demonstrated in the retinas of the pre-immunized animals 60 days after exposure to laser. The diameter of the lesion was 356 μm as compared with 406 μm (P < 0.01), the cell density of the photoreceptor cell bodies measured in the whole lesion was 72.4% of normal as compared with 64.5% (P = 0.01), and at the center of the lesion it was 57.3% of normal as compared with 38.2% (P < 0.01) (treated and control groups, respectively). Conclusions  Immunization with PN-277 has an ameliorative effect in neural tissue such as the retina. This type of immunization may be of clinical significance in reducing laser-induced retinal injuries in humans. Shiri Shulman and Mark Belokopytov contributed equally to this work.     

Role of the vitreous in retinal neovascularization evaluated by a comparison of central retinal vein occlusion and branch retinal vein occlusion

Thirty three patients (33 eyes) with central retinal vein occlusion (CRVO) and 80 patients (81 eyes) with branch retinal vein occlusion (BRVO) were studied in an attempt to investigate the role of the vitreous in the formation of retinal neovascularization. All these eyes had some areas of capillary nonperfusion confirmed by fluorescein angiography and no scatter photocoagulation before the first examination. The incidence of new vessels at the optic disc (NVD) in CRVO was not significantly different from that in BRVO. However, the incidence of new vessels elsewhere (NVE) in CRVO was significantly less than that in BRVO. Follow-up vitreous examination of 36 cases while they had not developed NVD and/or NVE showed a higher incidence of posterior vitreous detachment from the mid-peripheral retina (MP-PVD) in CRVO than in BRVO. On the other hand, there was no statistically significant difference in the incidence of posterior vitreous detachment from the optic disk (D-PVD) between CRVO and BRVO. The high incidence of MP-PVD in CRVO may explain the low incidence of NVE in CRVO.     

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).     

Colour Doppler assessment of blood flow in eyes with central retinal vein occlusion

PURPOSE: To assess the blood flow changes in eyes with central retinal vein occlusion (CRVO) and compare these values with values of fellow eyes and eyes of normal subjects. METHODS: 25 eyes of 25 consecutive newly diagnosed patients with CRVO comprised the study group. Their fellow eyes and those of 25 healthy subjects were the control group. All patients underwent a complete ophthalmological examination. Eyes with CRVO were classified into two groups as non-ischaemic and ischaemic by fundus fluorescein angiography. Colour Doppler imaging was performed with a Toshiba Sonolayer SSH-140A and 7.5-MHz linear array probe. Maximum systolic velocity (V(max)), end-diastolic velocity (V(min)) and resistive index (R(i)) values were noted for each of the central retinal artery (CRA), central retinal vein (CRV) and ophthalmic artery (OA). These parameters were compared with those of the fellow eyes and both eyes of the control group. RESULTS: Mean ages were 63.55 and 61.45 years in the CRVO and control groups, respectively. Age and sex distributions were statistically identical in both groups. When we compared the eyes with CRVO to the control group, no statistically significant difference existed between the two groups with regard to the V(min) and R(i )values of the CRA and CRV. However, V(max ) values of the CRA and CRV were significantly lower in CRVO eyes when compared to the control group. The CRVO group and control group had similar V(max), V(min ) and R(i) values for the OA. Only the V(max) was significantly lower in the CRV in eyes with CRVO when compared to the unaffected fellow eyes. No statistically significant difference could be detected between any of the parameters of CRA, CRV and OA of the ischaemic and non-ischaemic CRVO groups. CONCLUSIONS: More data on broader series need to be obtained in order to decide on the practical use of colour Doppler imaging in the differentiation of ischaemic eyes from non-ischaemic eyes in CRVO.     

Retina tomography after vitrectomy for macular edema of central retinal vein occlusion

PURPOSE AND OBJECTIVE: To report retina tomography after vitrectomy for macular edema in central retinal vein occlusion (CRVO). PATIENTS AND METHODS: Five patients with macular edema caused by CRVO were examined using optical coherence tomography (OCT) through their clinical courses. RESULTS: The retinal thickness through the fixation was reduced in all 5 eyes. Preoperatively, the retina thickness at the foveola was more than 500 microm in three eyes and more than 1000 microm in 2 eyes. The retina thickness was reduced to 311+80 microm within two weeks on average. Visual acuity was improved by two or more lines in 3 of 5 eyes. CONCLUSION: Vitrectomy is worthy of consideration when macular edemas are prolonged in patients of CRVO. OCT is a useful instrument for management and treatment of macular edema.     

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.     

Choroidal circulatory disturbances associated with retinal angiomatous proliferation on indocyanine green angiography

Purpose To investigate the association between choroidal perfusion and retinal angiomatous proliferation (RAP). Methods We performed indocyanine green angiography (ICGA) on 26 eyes of 13 consecutive patients with RAP, and 17 eyes of 17 age-matched controls without age-related macular degeneration. In eyes with RAP and concurrent pigment epithelial detachments (PEDs), we evaluated ICGA images obtained after the PEDs resolved following treatment. Of the 26 eyes in the study group, five eyes with stage 3 RAP or a disciform scar and two eyes that underwent photodynamic therapy were excluded from further evaluation, leaving 19 eyes (11 eyes with stage 1 or 2 RAP and eight fellow eyes without RAP). Results Early decreased choroidal filling (EDCF) was observed in nine (81.8%) of 11 eyes with RAP and five (62.5%) of eight fellow eyes without RAP. Late decreased choroidal filling (LDCF) occurred in nine (81.8%) of 11 eyes with RAP and four (50%) of eight fellow eyes without RAP. The incidence of EDCF and LDCF was significantly higher in eyes with RAP than in the control eyes (p < 0.05, p < 0.01, respectively). Conclusions Persistent decreased choroidal filling is common in early-stage RAP. Clinicians should be aware of this, especially when considering treatment. The authors have no financial interest in any aspect of this study.