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Purpose: To investigate the efficacy of intravitreal bevacizumab (IVB) for neovascular age-related macular degeneration (AMD)., Methods: We conducted a retrospective study of 29 eyes of 29 patients with AMD (19 eyes) and polypoidal choroidal vasculopathy (PCV; 10 eyes), who were followed up at least 1 year after the initial IVB (1.0 mg/0.04 ml). The eyes were classified according to the lesion type and size. Best-corrected visual acuity (BCVA) and central retinal thickness were examined before and 3 months, 6 months and 12 months after the IVB., Results: The mean application times of IVB were 2.1 in 1 year. When classifying the eyes according to the lesion type, BCVA improved in 5 (26.3%) eyes with AMD and 1 (10.0%) eye with PCV by over 0.2 logarithmic minimum angle of resolution (logMAR) units. The BCVA decreased significantly 1 year after the IVB in eyes with PCV (p = 0.032). When classifying the eyes according to the lesion size, BCVA improved by over 0.2 logMAR units in the 4 (50.0%) eyes with a size of less than 1 disc diameter, 1 (10.0%) eye with the size of 1 to 3 disc diameters, and 1 (9.1%) eye with the size of over 4 disc diameters. The BCVA decreased significantly 1 year after the IVB in the eyes with the size of 1 to 3 disc diameters and with the size of over 4 disc diameters (p = 0.028, 0.013, respectively). The central retinal thickness did not change significantly at any time point compared to that before the IVB., Conclusions: These results suggest that IVB may be efficacious in preserving visual acuity in AMD eyes and in eyes with the size of less than 1 disc diameter.

Purpose: To investigate the effectiveness of intravitreal administration of bevacizumab (IVB) for choroidal neovascularization (CNV) in retinal angioid streaks (AS)., Subjects and Methods: Five eyes of four subjects with CNV in AS were observed for an average followup period of 12 months. The average greatest linear diameter (GLD) of the AS was 4315 microm before treatment. IVB (1.0 mg or 1.25 mg) was performed a total of two times at eight week intervals, and additional bevacizumab was administered whenever exudative changes occurred., Results: Visual acuity improved in one eye (20%), was maintained in two eyes (40%), and worsened in two eyes (40%). Recurrence of CNV was observed in two eyes (40%). Before treatment, the GLD was 2439, 2844, and 3654 microm in the three eyes in which visual acuity was maintained, and 5803 and 6837 microm in the two eyes with worsened visual acuity. Recurrence of CNV was observed in the two eyes with worsened visual acuity., Conclusion: Short-term CNV fibrosis and maintenance of visual acuity were achieved with IVB in cases in which the GLD was less than 3500 microm.

Background: Stickler syndrome is an autosomal dominant disease characterized by various disorders of the eyes and the connective tissues throughout the body. It can arise from a mutation in the collagen associated gene. We present a case of Stickler syndrome with rhegmatogenous retinal detachment., Case: A 10-years-old boy was referred to us with rhegmatogenous retinal detachment of the right eye. His family history included eye disease and a cleft palate. He had high myopia, vitreous liquefaction and lattice degeneration in the both eye. He also had a cleft palate and a broad nasal bridge. His condition was diagnosed as Stickler syndrome. We performed vitrectomy, scleral buckling and encircling, and silicone oil injection in the right eye. We also did a reattachment of the retina in the right eye., Conclusions: Pediatric retinal detachment may indicate the presence of Stickler syndrome and a complete examination of the eye as well as a full family history must be obtained in such cases.

Purpose: To examine the short-term effects of intravitreal injections of bevacizumab on macular edema due to central retinal vein occlusion (CRVO)., Methods: Twenty one eyes of 21 consecutive patients with macular edema due to CRVO were included. The patients received intravitreal injections of 1.25 mg bevacizumab at the initial examination. They were followed up with best-corrected visual acuity (BVCA), fluorescein angiography, and central macular thickness (CMT) by optical coherence tomography for more than 4 months. Whenever the macular edema recurred, another intravitreal bevacizumab was given., Results: The mean age of the patients was 68.1 +/- 11.8 and the mean follow up was 6.5 +/- 2.6 months. The mean baseline BVCA (logMAR) and CMT were 0.79 +/- 0.45 and 699 +/- 194 microm, respectively. After treatment, the mean BVCA improved significantly at 1 week (0.52 +/- 0.46, p<0.001), 1 month (0.48 +/- 0.46, p<0.001), 2 months(0.56 +/- 0.43, p<0.02), and 4 months (0.51 +/- 0.47, p<0.001). The mean CMT also decreased significantly at 1 week (296 +/- 86 microm, p<0.001), 1 month (286 +/-132 microm, p<0.001), 2 months (464 +/- 249 microm, p<0.05) and 4 months (362 +/- 198 microm, p<0.001). Similar effects on reducing CMT were obtained both after the initial injection and the second injection of bevacizumab., Conclusion: Intravitreal injection of bevacizumab improved visual acuity and macular edema due to CRVO.

Purpose: To study the effect of intravitreal bevacizumab on macular edema secondary to branch retinal vein occlusion (BRVO)., Subjects and Methods: 6 eyes of 5 patients averaging 70 years, who had received either retinal photocoagulation or trans-tenon retrobulbar triamcinolone injections or both, but in whom the macular edema remained. There was an average of 337 days from BRVO onset to injection of bevacizumab. Corrected vision and foveal thickness were measured., Results: Visual acuity and foveal thickness improved significantly one month after injection., Conclusion: Intravitreal injection of bevacizumab is effective for a short time.

Purpose: To evaluate the effects of intravitreal injection of tissue plasminogen activator (tPA) on central retinal vein occlusion(CRVO) associated with diabetic retinopathy (DR)., Methods: A retrospective study of 42 eyes of 42 patients(mean age: 68 years, female/male = 20/22, 5 eyes associated with DR) with macular edema caused by CRVO treated with tPA. Best corrected visual acuity (BVCA or logarithm of the minimal angle of resolution: logMAR), macular thickness was mea sured by optical coherence tomography (OCT), and several variables were evaluated., Results: The mean logMAR and macular thickness improved significantly in the DR (-) group, but, no significant changes were observed in the DR (+) group. Post-operative posterior vitreous detachment (PVD) developed in 62% of the DR (-) group and none of the DR (+) group., Conclusion: There may be no beneficial effects of intravitreal tPA on CRVO associated with diabetic retinopathy.

A 57-year-old man was admitted to our hospital because of persistent blurred vision for 5 months. He had opacity in the vitreous body and white lesions in the retina of the right eye. Although cytological examinations of the vitreous samples revealed Class II, the diagnosis of primary intraocular lymphoma (PIOL) was made by detecting both IgH rearrangement by PCR and an elevated ratio of IL-10/IL-6 concentration in the vitreous sample. Systemic examinations were performed simultaneously and no extra-ocular involvement was detected. Intravitreal methotrexate (MTX) injections were effective and the lesions disappeared following injections. Two months later (10 months after appearance of the right eye lesion), however, the same lesions appeared in the left eye. Cytological examinations of the left vitreous sample revealed Class V by detecting large abnormal lymphocytes. Although intravitreal MTX injections were also effective, central nervous system (CNS) involvement appeared only 2 months after the left eye lesions appeared. Open biopsy was performed and a diagnosis of diffuse large B-cell lymphoma was made. Despite starting with high-dose MTX, he died of CNS disease 1 year and 8 months after onset. Diagnosis of PIOL is difficult. Since local treatment was considered insufficient, an optimal treatment strategy for PIOL should be established.

Despite considerable recent advances in vitreoretinal surgery, generally performed in more advanced stages of diabetic vitreoretinopathy (DVR), a satisfying visual acuity cannot always be achieved. Even in the early DVR stages that might be detected by routine eye exams, management of general factors, such as blood glucose concentration and blood pressure, currently constitutes the only proven preventive measures. New approaches for amelioration and treatment of DVR are needed. The Hisayama study, an ongoing prospective cohort study of cardiovascular disease and its risk factors in a community in Hisayama Town adjoining Fukuoka City, revealed that the cut-off point for diagnostic fasting glucose level is lower (116 mg/dl) than that of the current diagnostic criteria (126 mg/ dl), indicating that more rigid diagnostic criteria might reduce the incidence of DVR in the Japanese population. In early stages of DVR, leukocyte adhesion in the retinal microvasuculature substantially contributes to DVR. We investigated the involvement of the Rho/ ROCK pathway in diabetic microvasculopathy and the therapeutic potential of fasudil, a selective ROCK inhibitor, and demonstrated that the Rho/ROCK pathway plays a critical role in leukocyte adhesion in diabetic retinal microvasculature and endothelial damage. Fasudil protects the vascular endothelium at least in part by inhibiting neutrophil adhesion and reducing neutrophil-induced endothelial injury via endothelial nitric oxide. In later stages of DVR, namely proliferative diabetic retinopathy, tractional retinal detachment associated with a cicatrical contraction of proliferative membranes can cause severe vision loss. We demonstrated the possible involvement of hyalocytes in proliferative membrane formation and its contraction mainly mediated through the function of TGF-beta 2 resulting in myofibroblastic transdifferentiation and phosphorylation of the myosin light chain, a downstream mediator of ROCK. ROCK inhibition by fasudil or statins successfully inhibited cicatrical contraction of the proliferative membranes both in vitro and in vivo. Further studies for direct evidence demonstrating whether altered diagnostic criteria of diabetes may lead to a lower incidence of DVR and determination of the therapeutic potential of ROCK inhibition in the clinic could provide new avenues of intervention for inhibiting DVR.

Purpose: To evaluate the safety and efficacy of intravitreal administration of pegaptanib sodium in Japanese patients with age-related macular degeneration associated with subfoveal choroidal neovascularization., Methods: Ninety-five male and female patients (mean age 72.5 years.) were assigned randomly in a double-masked manner to receive 0.3 or 1 mg of pegaptanib sodium every 6 weeks over a 48-week period. Efficacy was assessed by visual acuity change from baseline as the proportion of patients who lost fewer than 15 letters at week 54 using the Early Treatment Diabetic Retinopathy Study chart., Results: The group that received 0.3 mg pegaptanib experienced a mean loss of 3.8 letters; 78.7% (37/47) of patients lost fewer than 15 letters. The 1 mg group had a change of -4.3 letters and the proportion that lost 15 letters was 72.9% (35/48). The proportion of patients whose visual acuity was unchanged or improved was 46.8% (22/47) and 43.8% (21/48) in the 0.3 and 1 mg groups, respectively. The majority of adverse events with possible, probable, or unknown relationship to pegaptanib were related to the intravitreal injection, such as mild conjunctival hemorrhage (0.3 mg: 76.6%, 1 mg: 77.1%) and superficial punctuate keratitis by sterilization (0.3 mg: 29.8%, 1 mg: 39.6%) at the injection site. Compliance with the study treatment of 9 intravitre al injections was as high as 87.2% and 85.4% for patients receiving 0.3 and 1 mg, respectively., Conclusion: Intravitreal injection of sodium pegaptanib every 6 weeks produced clinically significant stabilization of visual acuity for one year in more than 70% of patients with age-related macular degeneration, with good treatment compliance.

Purpose: To investigate the 1-year results of treatment for retinal angiomatous proliferation (RAP), especially focused on the combination therapy of intravitreal injection of tiamcinolone acetonide with photodynamic therapy (IVTA-PDT)., Methods: Between July 2004 and July 2005, IVTA-PDT was performed in 7 patients (9 eyes) with RAP at the Ohtsuka Eye Hospital. We reviewed the records of 4 of these patients (5 eyes) who had received IVTA-PDT during follow-up., Results: PDT was effective in only 1 of the 9 eyes. During IVTA-PDT, leakage from neovascularization was observed on angiography, and retinal edema and retinal pigment epithelial detachment (RPED) were observed on optical coherence tomography (OCT), even though PDT had been performed several times in all 5 eyes receiving IVTA-PDT. Complete resolution of angiographic leakage and improvement of retinal edema and RPED were observed at the examination 3 months after IVTA-PDT. At 1 year after IVTA-PDT, the fundus findings remained stable in 4 eyes, but angiographic leakage and RPED had progressed slightly in one eye. Visual acuity 1 year after IVTA had decreased compared with that at the primary PDT, but was almost the same as that at the beginning of IVTA-PDT., Conclusions: IVTA-PDT for eyes with RAP, in which PDT had been performed several times, may be effective for improvement or elimination of retinal edema, achieving rapid regression of neovascularization, and stabilizing visual acuity.

Purpose: To evaluate the efficacy of intravitreal gas injection for submacular hemorrhages(SMH)., Patients and Methods: The records of 29 patients with SMH, who were treated by pneumatic displacement with expansile gas, were reviewed retrospectively., Result: In observable cases, SMH had started moving within five days after the procedure. After 6 months visual acuity had been improved 2 or more lines in 23 eyes(79%). The causes of SMH were age-related macular degeneration (17 eyes) and microaneurysm (12 eyes). The larger the size of SMH, had the greater the risk of developing vitreous hemorrhage. Twelve eyes of the 29 eyes required vitrectomy owing to vitreous hemorrhage, insufficient removal of SMH, etc. but this pneumatic procedure often eliminated the need for vitrectomy. The visual acuity of the patients with additional vitrectomy was improved with only pneumatic displacement. None of the patients had serious complications with this pneumatic procedure and the vitrectomy., Conclusion: The first choice for SMH is intravitreal gas injection which saves foveal function, and improves the prognosis for better vision.

Purpose: To report the efficacy of intravitreal injection of triamcinolone acetonide(TA) for cystoid macular edema remaining after vitreous surgery., Methods: Eight eyes of 7 patients aged from 32 to 84 years old were studied. The original diseases that caused macular edema were central retinal vein occlusion in 2 eyes, branch retinal vein occlusion in one eye, Irvine-Gass syndrome in 2 eyes, and diabetic retinopathy in 3 eyes. 4 mg of TA was injected intravitreally and visual acuity and foveal thickness measured by optical coherence tomography(OCT) were evaluated in before and after the surgery., Results: Macular edema resolved rapidly after injection of TA in all cases and cysts were extinguished or diminished. The foveal thickness in OCT was reduced significantly from preoperative 495 +/- 116 (mean +/- standard deviation) microns to 267 +/- 117 microns after one week, and 246 +/- 81 microns after one month. The effect persisted for three months. Visual improvement of more than two Snellen lines was seen in 4 eyes. No side effects were observed except a temporary increase of intraocular pressure in one eye., Conclusion: Intravitreal injection of TA is effective in a short-term for cystoid macular edema remaining after vitrectomy.

Background: Indirect choroidal rupture due to blunt ocular trauma involves rupture of the choriocapillaris or the full thickness of the choroid and Bruch's membrane. The overlying retinal pigment epithelium and the sensory retina are usually intact or atrophic, but rarely ruptured. We report a case of choroidal rupture healed with proliferative tissue protruding through the sensory retina into the vitreous cavity., Case: A 22-year-old man was punched in the left eye. Hypotony maculopathy and choroidal rupture passing through the macula were noted., Results: The intraocular pressure was normalized after suturing of the dialyzed ciliary body to the sclera and hypotony maculopathy was cured. Proliferative tissue formation protruding through the sensory retina into the vitreous cavity was observed 1 month after the injury. Corrected visual acuity was improved from 0.09 to 0.6. Optical coherence tomography showed that the site of the proliferative tissue was located immediately temporal to the fovea and that the fovea kept its normal form., Conclusion: Optical coherence tomography was useful in monitoring the morphological change in the macula and predicting visual acuity in a case of blunt ocular trauma involving the macular area.

Polyvinylacohol (PVA) gel cross linked by gamma irradiation was assessed as a possible vitreous substitute. In our previous, reports, elevation of intraocular pressure and inflammatory changes in the vitreous cavity after operation were observed in some of the experimental animals. Four types of PVA gel (sol) were produced by a newly refined method. We improved the gel systhesis process to remove the monomer and contamination. Colored rabbits were used for this experiment. Vitreous replacement was performed after vitrectomy. This was followed clinically by ophthalmoscopy, tonometry, fundus photography, electroretinogram, chemotaxis, and laser-flare-cell-metering. Histopathological examination by light microscopy was performed after 3 months. PVA gel has good biocompatibility in the vitreous cavity, and gel with a network similar to that of the vitreous body showed the best biocompatibility. Although it is necessary to investigate the biocompatibility over the long term and to evaluate the tamponade effect, PVA gel will be a bood candidate for a vitreous substitute.

This review describes the techniques to evaluate retinal neurodegeneration induced by excitatory amino acids and transient ischemia. Glutamate-induced neurotoxicity was examined in cultured rat cortical cells. Cultures obtained from the retinas of fetal rats were incubated in Eagle's minimal essential medium supplemented with 10% fetal calf serum or 10% horse serum at 37 degrees C in a humidified 5% CO2 atmosphere for 10-14 days. The neurotoxicity induced by glutamate was quantified by trypan blue exclusion. The viability of cultures was markedly reduced by a 10-min exposure to glutamate followed by incubation with glutamate-free medium for 1 hr. N-methyl-D-aspartate (NMDA)-induced retinal damage was examined in adult rats. Transverse sections of the retinas through the optic disk were stained with hematoxylin and eosin. A single intravitreal injection of NMDA damaged the ganglion cell layer and the inner plexiform layer without affecting the other retinal layers 7 days after injection. Retinal ischemia was induced by elevating the intraocular pressure for 45 min through the needle which was placed in the anterior chamber. Ischemia-induced retinal damage was inhibited by MK-801. These results indicate that the techniques described in this review can be employed to develop new drugs possessing neuroprotective action against neurodegeneration that occurs during retinal ischemia.

Experimental epiretinal membranes (ERM) composed of Müller cells were formed by injecting autologous whole blood into the vitreous cavity of rabbits. Müller cell responses at the early stages of epiretinal membrane formation were studied using immunostaining of proliferative cell nuclear antigen (PCNA) (for identification of the proliferating cells) and glial fibrillary acidic protein (GFAP) (as an appropriate marker for glial cell response), and the electron microscope in the experimental rabbit model. Three days after the injection, nuclei of Müller cells were found in the inner part of the retina and were PCNA positive. PCNA positive staining was seen from day 3 to day 7. No PCNA-positive nuclei were seen at day 14 in the retina or ERM. A GFAP-positive reaction was first seen in the inner retina at day 3. Afterwards, the retina and the ERM were GFAP-positive in the experimental period. We concluded that activation and proliferation of Müller cells began at an early stage after the blood injection. Müller cells remained active and expanded onto the retinal surface.

A patient with systemic lupus erythematosus (SLE) developed bilateral cytomegalovirus (CMV) retinitis and was treated with a total of 9 intravitreal ganciclovir injections at a dose of 400 micrograms/50 microliters in each eye under topical anesthesia. She was unable to receive systemic antiviral therapy because of bone marrow suppression and renal failure. The condition of both eyes improved after the intravitreal injections. Recurrence of CMV retinitis was not seen until death. Intravitreal injections of ganciclovir are useful even for the non-acquired immunodeficiency syndrome (AIDS) immunocompromised patients with CMV retinitis when the patients can not receive intravenous medications because of systemic complications.

The therapeutic effects and safety of intravitreal ganciclovir injection were evaluated in 16 acquired immunodeficiency syndrome (AIDS) patients with cytomegalovirus (CMV) retinitis. The induction therapy was done in a total of 23 courses, i.e., in 14 eyes of 10 patients. Active lesions of CMV retinitis were suppressed by 3 to 7 injections over 21 to 42 days after the initiation of the induction therapy. Intravitreal injections once a week for maintenance suppressed the reactivation of the lesions for at least 6 weeks in 9 eyes of 7 patients among 10 eyes of 8 patients. As for the safety of intravitreal ganciclovir injections in the 16 AIDS patients with CMV retinitis, a total of 354 injections were given and two serious complications, that is, endophthalmitis and retinal detachment were observed in one eye each. During the course of intravitreal injection, 3 of 7 patients developed CMV retinitis in the contralateral eye and systemic CMV infections were suspected in 3 of 12 patients. Intravitreal injection of ganciclovir is thought to be effective for the treatment of CMV retinitis in AIDS patients, but careful procedure and examinations are needed.

Effects of intravitreal injection of levofloxacin (LVFX) on the electroretinogram (ERG), visual evoked potential (VEP), and retinal histology were studied in 23 albino and 23 pigmented rabbits to establish the non-toxic intravitreal dosage of LVFX. Doses of 200, 500, 1,000 or 2,000 micrograms of LVFX were injected intravitreally. The ERG and VEP were recorded before injection, and 3 hours, 2 days, 1 week, 2 weeks and 4 weeks after injection. The oscillatory potential transiently deteriorated with 1,000 and 2,000 micrograms doses of LVFX in albino and pigmented rabbits. No ERG changes were observed with 200 and 500 micrograms doses. No abnormal changes were observed in the VEP or retinal histology with any doses of LVFX. These results indicate that intravitreal injections of 200 and 500 micrograms of LVFX are nontoxic to the rabbit retina.

Effects of an intravitreal injection of melphalan on the electroretinogram and on the retinal structure were studied in albino rabbits to establish the non-toxic dose for its intravitreal use. The a-wave, the b-wave, the c-wave, the oscillatory potential and the retinal structure remained unchanged after 10-micrograms injection, but moderately changed after 20-micrograms injection and greatly deteriorated after 90-micrograms injection. A 10-micrograms injection is equal to an intravitreal concentration of about 5.9 micrograms/ml, if evenly diffused in the rabbit vitreous. Considering that colony formation of in vitro retinoblastoma cells is completely suppressed by melphalan at 4 micrograms/ml concentration, an intravitreal application of melphalan could be used as a non-surgical treatment for retinoblastoma.

We studied the anterior chamber inflammation with a laser flaremeter after transvitreal membrane peeling surgery for posterior vitreous membrane syndrome and cataract intraocular lens surgery, through separate surgery and combined surgery. In 16 eyes with vitrectomy and membrane peeling, mean flare count had one peak of 11 photons/msec at postoperative days 5 through 7. In 10 eyes with phacoemulsification and aspiration with posterior chamber lens implantation, the mean flare count had two peaks of 11 photons/msec at postoperative day 1 and in postoperative week 2. In 25 eyes with combined surgery of vitrectomy and cataract intraocular lens surgery, the mean flare count was similar to the summation of that of each simple surgery. In these 25 eyes, in 9 eyes with sutures, the mean flare count had two peaks of 37 photons/msec at postoperative day 1 and 27 photons/msec at postoperative week 2, and in 16 eyes with self sealing wounds, the mean flare count had one peak of 22 photons/msec at postoperative week two. In 14 vitrectomized eyes with cataract-intraocular lens surgery, the mean flare count was as high as in combined surgery. In eyes with self sealing wounds, the flare count at postoperative day one was significantly lower than that of sutured eyes.

We report ocular findings from 2 children with Kniest dysplasia. Both eyes of the 2 patients had abnormal long axial length causing high myopia, and vitreoretinal degeneration. The vitreous cavity of case 1 (a 15-year-old boy) which contained fibrous clouded membranous structures floating in the retrolental space and dense opacity at the temporal-inferior portion, was optically empty. Case 2 (a 7-year-old boy) had cortical and posterior subcapsular opacity of the lens, and also veil-like vitreous opacity in the periphery. Their common retinal changes were characterized as perivascular lattice degeneration and white without pressure in various degrees. They have not yet shown cataract or retinal detachment which needs surgical treatment, but close ophthalmological follow up will be necessary for their favorable prognosis. The literature on vitreoretinal degeneration such as Wagner's disease or Stickler syndrome may indicate the relation of Kniest dysplasia to similar diseases. Because they might have different clinical courses and visual prognosis according to the original biosynthetic disorders, we emphasized the importance of orthopedic diagnosis regarding such vitreoretinal degeneration with constitutional bone diseases.

We report a 26 year-old male patient who had floaters and hyperemia in his left eye following uveitis due to gnathostoma that had migrated into the vitreous cavity. Severe iridocyclitis and mild opacity of the vitreous body were observed, together with whitish-yellow subretinal tracks accompanied by dot and blot hemorrhages in the fundus. Slit lamp microscopic examination revealed a worm which writhed in the vitreous cavity. We performed vitrectomy to remove the worm from the anterior vitreous uneventfully, followed by prompt subsidence of the inflammatory signs. The worm was identified as a third instar larva of Gnathostoma doloresi. Eosinophilia and creeping eruption did not appear throughout the follow-up period. The patient was accustomed to eat live roaches and whitebait, as well as sliced raw beef liver.

Endothelin-1 (ET-1) reduces intraocular pressure (IOP) in animals when administered topically. The time course of IOP induced by ET-1, however, has not been fully elucidated. We studied the IOP response to different doses of ET-1 ranging from 10(-7) to 10(-4)M (5 micrograms to 5 ng) intravitreally injected in rabbits. In each animal one eyes received 20 microliters of ET-1 solution and the contralateral eye received same amount of vehicle in a randomized, masked fashion. IOP was measured by a pneumotonometer prior to and periodically for at least 72 hours after the intravitreal injection. ET-1 in 10(-4) and 10(-5) molar concentration elicited a biphasic IOP response consisting of an initial rise of 1 to 2 hours duration, and a subsequent prolonged reduction lasting for more than 72 hours. 3 x 10(-6) and 10(-6) M solution resulted in a prolonged IOP reduction without an early IOP rise. No significant IOP change was induced by 10(-7) M solution or vehicle. Both IOP rise and reduction were significantly related to the dose of ET-1.

Experimental retinal detachment was produced by injecting various fluids into the subretinal space in pigmented rabbits. We selected autologous aqueous humor, autologous vitreous, and autoserum as substitutes for subretinal fluid. Retinal detachment disappeared within 24 hours. The eyes were enucleated 7 days after surgery for histopathological study. Destructive changes in photoreceptor layer occurred most severely when the eye was treated with serum. There was a decrease in the number of outer nuclear layer cells. Macrophages and fibroblastic cells had migrated into the subretinal space. Histopathological changes with vitreous were less pronounced than with serum. The cytoplasm of Mueller cells appeared to compensate for the loss of photoreceptor cells in the outer nuclear layer. Mild decrease in the number of photoreceptor cells was the sole pathological feature when the eye was treated with aqueous humor. The retina thus showed different reactions to the subretinal fluids of differing nature.

We reported previously selective damage of the outer segment of the photoreceptors and retinal pigment epithelium after intravitreal injection of netilmicin sulfate in the rabbit. The cellular damage was thought due to active damage of phospholipase C enzyme, preventing it from performing phospholipid inositol metabolism, and to the presence of calcium. Therefore we investigated the retinal damage following after intravitreal injection of calcium and netilmicin sulfate in the rabbit. Morphologically, the retina did not show any structural change after intravitreal injection of CaCl2 at any concentration. After an intravitreal injection of netilmicin sulfate mixed with CaCl2, the damage in the photoreceptor outer segment was reduced at a concentration of 200 micrograms/0.1 ml and in the retinal pigment epithelium at a concentration of 1,000 micrograms/0.1 ml. This showed that retinal damage due to netilmicin sulfate can be reduced by the addition of calcium.

Endothelin, a novel, potent, and long-acting vasoconstrictor peptide, is thought to regulate retinal circulation and its autoregulation. A disturbance in the regulation of endothelin production might contribute to the pathogenesis of retinochoroidal or optic nerve diseases. We examined the effects of endothelin on the retina and the optic nerve using the electroretinogram (ERG) and visual evoked potential (VEP). Six male albino rabbits underwent intravitreal injection of 0.1 ml (10(-5) mol/l) endothelin-1 in the right eye. Six other male albino rabbits, which were injected intravitreally with 0.1 ml of Opeguard-MA in the right eye, were used as controls. Endothelin-1 caused marked constriction of retinal vessels and pallor of the optic nerve head. These findings persisted for 10 days after endothelin-1 injection. The amplitude of the b-wave and the latency of the oscillatory potential in the ERG were not significantly different from those in controls. On the other hand, prolongation of the VEP-N1 latency was observed for 14 days after the injection. These results indicate that endothelin acts on the circulation of the optic nerve head rather than that of the retina, and that effects persist for a relatively long period.

We reported previously that intravitreal injection of a small amount of 1-ornithine hydrochloride in monkey eyes damages the retinal pigment epithelium (RPE), selectively. At one year after administration, sharply demarcated chorioretinal atrophy was seen. This paper describes the intermediate stage of retinal degeneration caused by ornithine. Two weeks following intravitreal injection of ornithine, RPE cells at the equator became necrotic and disappeared. However RPE regenerated to cover Bruch's membrane at the border of RPE degenerated area. In 2 months at an area where RPE cells disappeared, the photoreceptors and choriocapillaris degenerated to disappear. However, in the area in where RPE regenerated, they maintained their structure. This report demonstrated that damage of RPE resulted in disappearance of the photoreceptor and choriocapillaris.

The retinal toxicity of intravitreally injected steroids, fluorometholone and tetrahydrocortisol, was examined. The concentration of the steroids was 20 mg/ml, and 0.05 ml of each solution were injected into the rabbit vitreous cavity. An equal volume of saline solution was injected as a control. In addition to ophthalmoscopy, intraocular pressure was measured and electroretinography, light microscopy and electron microscopy were performed. The results showed no remarkable changes in all eyes. Fluorometholone and tetrahydrocortisol seem to have neither toxicity to the retina nor adverse effect of elevating intraocular pressure when intravitreally injected with this amount.

Using adult albino rabbits, the clinical course of lens opacity and morphological changes of lens epithelial cells were observed from 2 weeks to 3 months after intravitreal silicone oil injection. Simple vitrectomy was performed in both rabbit eyes. One eye with silicone oil injection served as an experimental eye, while another control eye did not receive any injection. Seven examined eyes showed early posterior subcapsular lens opacity from one month after silicone oil injection by slit-lamp microscopy. Small intracellular vacuoles near to the interdigitation of the lens epithelial cells were observed in the 7 eyes from 2 weeks after the procedure by transmission electron microscopy. These changes were not observed in 7 control eyes. As a result, it is surmised that cataract formation after intravitreal silicone oil injection may be associated with morphological changes of the lens epithelial cells.

Endothelins (ETs), which are one of the most potent vasoconstrictors, were discovered in 1988. ETs are involved in the regulation of vascular smooth muscle and are thought to function like a local hormone. In this study, we measured changes in the caliber of retinal blood vessels caused by the intravitreal injection of ET 1 in rabbits, using fundus photography. The retinal artery showed an immediate vasoconstriction after the injection (0.1 ml) of ET 1 at 10(-6)M. However, ET 1 in lower concentrations (10(-7)M and 10(-8)M) caused vasodilations initially and subsequently vasoconstrictions. A dose-response relation was found. The blood vessel caliber reduced maximumly to 53% the value before injection. The vasoconstriction due to ET 1 may induce retinal ischemia and hypoxia. We speculate that ET 1 may be involved in the regulation of retinal blood vessels.

The influence of intravitreal injection of a small amount of l-ornithine hydrochloride in monkey eyes has been investigated morphologically. In a previous paper, the author demonstrated that acute selective damage was caused in the retinal pigment epithelium (RPE) by ornithine. This paper will demonstrate retinal degeneration at the late stage by intravitreal injection of ornithine. At one year after administration, sharply demarcated chorioretinal atrophy was seen ophthalmoscopically from the equator to the peripheral retina. These areas corresponded to those where RPE became necrosis at early stage following administration of ornithine. Histopathologically, the photoreceptor cells, RPE, and choriocapillaris disappeared completely in these areas, and the inner retina was directly contact with the Bruch membrane with the proliferating Müller fibers. On the other hand at the posterior pole, the photoreceptor cells, RPE, and the choriocapillaris maintained intact. This study demonstrated that necrosis of RPE by intravitreal injection of ornithine leads to complete loss of the visual cells and choriocapillaris, at the late stage.

Morphological changes of the retina following one-shot injections into the vitreous of netilmicin sulfate were investigated. The concentrations of netilmicin in the vitreous after intravitreal injection showed the curve of y = a/xb, where y is the concentrations in the vitreous body, x in the number of days since injection and a, b are constant. Concentration decreased rapidly after the injection, and almost totally disappeared after one week. Morphologically, the retina showed normal structure following injections of 100 micrograms/0.1ml and 200 micrograms/0.1ml. Following injections of over 500 micrograms/0.1ml, the outer segment of the photoreceptor disappeared and many phagosomes appeared in the retinal pigment epithelium cell. Following one shot injections of over 500 micrograms/0.1ml damage to the photoreceptor and retinal pigment epithelium was demonstrated. The above data suggested that one-shot injection of netilmicin in concentrations of up to 200 micrograms/0.1ml could be mode without retinal damage.

The quantitative changes of the aqueous flare following intravitreous gas injection were determined by laser flare-cell metry in rabbits. A volume of 0.4 ml of air, 100% sulfur hexafluoride (SF6), or 100% perfluoropropane (C3F8), was injected separately into the vitreous of pigmented rabbits. The normal range of the aqueous flare was 7.8 +/- 3.0 (photon counts/msec). Each model showed an increase of aqueous flare on the first day (air: 18.9 +/- 9.1, SF6: 19.5 +/- 11.5, C3F8: 40.8 +/- 22.8). Subsequently, the aqueous flare of air-injected eyes gradually decreased, while that of SF6-injected eyes increased on the 4th day, and then gradually decreased. Also that of C3F8-injected eyes increased on the 4th day, and the 7th day, then decreased on the 14th day, but it was still higher than normal. Cataracts developed in two of the five eyes injected with SF6 and all of the four eyes injected with C3F8. These findings revealed that following intravitreous gas injection, disruption of the blood-ocular barrier depended on the expansibility of the gas and the length of time it remained in the vitreous cavity.

Retinal damage 1 to 7 days after intravitreal injection of 1-ornithine hydrochloride solution into monkey eyes was investigated. Clinically the retinal pigment epithelium (RPE) showed edema, and hyperfluorescence on fluoroangiograms, predominantly in the equatorial region at 3 to 7 days. No retinal changes were seen at the posterior pole. Histopathologically, RPE in the equatorial region showed severe damage 24 hours after injection, becoming liquefactively necrotic and degenerated at 3 to 7 days. Early changes in RPE consisted of an increase in the number of secondary lysosomes, disappearance of basal infolding, destruction of most of the smooth endoplasmic reticulum, shortening of microvilli, and marked swelling of mitochondria. These RPE changes were seen slightly in the posterior pole. There were slight changes in the inner retina including photoreceptors. In eyes injected intravitreally by hi-osmosis of 3.5% NaCl solution, with equivalent osmolarity to ornithine solution, mild changes of microvilli and mitochondria were seen, but not necrotic changes. Our experiment showed that intravitreal injection of a small amount of 1-ornithine hydrochloride induced severe RPE damage. Selective toxicity of ornithine to RPE appeared mainly in the equatorial region.

A case of intraocular and brain malignant lymphoma was presented in which histopathological and immunohistochemical analysis of the necropsy eyes and brain lesions were performed. Lymphoma cells infiltrated into both eyes and the brain. The tumor cells could be found only in the vitreous cavity, not in other ocular tissues. Lymphoma cells were morphologically better preserved in the vitreous cavity, than in the vitrectomized specimen. Applying immunoperoxidase techniques to the necropsy eyes and brain lesions, the lymphoma cells were identified a B cell type, and the diagnosis of vitreous biopsy specimen was confirmed.

The present work was undertaken to evaluate the effect of sulfur hexafluoride (SF6) injected intravitreously in rabbit eyes. The alterations of the outer blood retinal barrier that was composed of anionic sites, using a cationic probe, polyethyleneimine (PEI). We injected 0.5 ml of 100% SF6 or 0.5 ml of air into the vitreous cavity of rabbit eyes, and the 0.5% PEI-saline solution was given intravenously at 2, 4, 7, or 14 days after the injection. Control eyes demonstrated numerous PEI-positive sites at the basement membrane of the RPE, collagen fiber of Bruch's membrane, and basement membrane of choriocapillaries. Until seven days after SF6 injection, PEI-positive sites decreased, but had increased at 14 days to control levels, while in air-injected eyes, they had recovered at seven days. SF6 in the vitreous was absorbed in seven days and air in three days. While gas was present in the vitreous, the charge barrier of the outer retina and choroid decreased, but when the gas was absorbed, the charge barrier recovered. The result showed that the decrease of charge barrier was a reversible change.

The membranes from 42 eyes with PDR and 8 eyes with PVR were removed during vitreous surgery. In 12 of those with PDR and 3 of the cases with PVR, the reproliferated membranes formed beneath silicone oil (SO) were removed and were histologically and immunohistochemically examined, using morphometrical quantitative analysis. In each case, area coefficient, fibrous content and the number of new vessels, and thick basement membranes, increased wall cells and multilayer basement membranes of new vessels were studied. In both PDR and PVR, the number of cells per unit area tended to be increased with the period of time after SO was injected, while the percentage of fibrous components did not change. The Percentage of occurrence of each type of new vessels was almost the same in both primary and reproliferative PDR membranes. In the primary proliferative PDR membranes, endothelial cell proliferation was found predominantly, while glial hyperplasia was predominant in the primary proliferated PVR membranes and the reproliferated membranes under SO of PDR and PVR.

We represent a case of vitreous hemorrhage due to subarachnoid hemorrhage from a ruptured aneurysm of the right vertebral artery to draw attention to this complication. A 53-year-old man was admitted to our hospital because of generalized headache and reduced visual acuity of both eyes. On admission the patient was alert and there were moderate nuchal stiffness and mild symmetrical hyperreflexia in the extremities. Ophthalmological consultation revealed bilateral retinal, subhyaloid and vitreous hemorrhages. Four-vessel angiography demonstrated an aneurysm of the right vertebral artery. At operation, it became clear that the aneurysm was a dissecting one. The vertebral artery was clipped at the most proximal intracranial portion. Postoperative course was smooth and uneventful except deteriorated visual acuity. His visual acuity deteriorated continuously to hand movements 18 days after subarachnoid hemorrhage. His visual acuity, however, gradually improved without specific treatment. At the time of this writing, his visual acuity is 1.0 on both sides. Vitreous hemorrhage is a rare complication following a reptured aneurysm. Pertinent literature concerning fundal hemorrhage, especially vitreous hemorrhage, associated with subarachnoid hemorrhage suggests that it may occur as a result of sudden increase of intracranial pressure.