Macular pucker formation after macular hole surgery with inverted internal limiting membrane flap technique and silicone oil tamponade.

PURPOSE: The inverted internal limiting membrane (ILM) technique was recently introduced for refractory macular hole. Here, we evaluate a case of macular pucker formation after macular hole surgery using the inverted ILM flap technique and silicone oil tamponade. After undergoing vitrectomy combined with ILM removal, the patient had a good visual prognosis. OBSERVATIONS: A 49-year-old male with macular hole affecting both of his eyes underwent vitrectomies. Three months after the first surgery in his right eye, macular pucker formation was observed in the macula, which was associated with the ILM flap used to cover the macular hole. After peeling the ILM, the macula returned to a normal contour and visual acuity improved. Examination of the removed ILM revealed macrophage-like cells containing silicone oil particles that were responsible for the ILM contraction. CONCLUSIONS AND IMPORTANCE: When using the inverted ILM flap technique and silicone oil, macular pucker may occur after macular hole surgery. Peeling of the ILM flap restored the macular shape and did not reopen the macular hole, thereby improving visual acuity. Thus, silicone oil should be used with caution when performing macular hole surgery with the ILM flap technique.

Plasmin-assisted vitrectomy for management of proliferative membrane in proliferative diabetic retinopathy: a pilot study.

PURPOSE: To demonstrate the feasibility of autologous plasmin for treatment of proliferative diabetic retinopathy. METHODS: The study examined prospectively six patients with bilateral proliferative diabetic retinopathy. Comparisons of the surgical time and the incidence of retinal tears were made between the eyes treated with autologous plasmin and their respective opposite eyes, which were treated without plasmin. RESULTS: All eyes treated with autologous plasmin required significantly less surgical time (68 versus 89 minutes, P = 0.04, paired t-test). In the plasmin group, no additional surgical procedures for removing the proliferative membrane were needed, including membrane delamination or segmentation. Moreover, with plasmin pretreatment, there were no retinal tears, which was in contrast to the control group, where three eyes with retinal tears were observed. There was no significant difference found between the two groups for final visual outcomes. CONCLUSION: Autologous plasmin may be beneficial in the surgical management of proliferative diabetic retinopathy.

Pitavastatin: protection against neuronal retinal damage induced by ischemia-reperfusion injury in rats.

PURPOSE: To evaluate the neuroprotective effects of pitavastatin against neuronal retinal damage induced by ischemia-reperfusion injury in rats. METHODS AND RESULTS: Ischemia-reperfusion injury was induced in Sprague-Dawley rats using ocular hypertension. Pitavastatin (0.1, 0.5, or 1.0 mg/kg) was given intravenously 12 hr or 5 min before, or 12 or 24 hr after the induction of ischemia-reperfusion injury. Morphometric and retrograde labeling analyses revealed neuroprotective effects when pitavastatin (0.5 mg/kg) was administered 5 min before--even 12 and 24 hr--after induction of ischemia-reperfusion injury. These effects depended on dose; protection was noted at pitavastatin concentrations of 0.5 and 1 mg/kg but not 0.1 mg/kg. Furthermore, preadministration of pitavastatin (0.5 mg/kg) reduced expression of P-selectin and intercellular adhesion molecule-1 at 12 and 24 hr after induction of ischemia-reperfusion injury. CONCLUSIONS: As pitavastatin was efficacious in preventing retinal neuronal death, it may be a novel therapeutic modality for ischemic retinal diseases.

Effect of pitavastatin on experimental choroidal neovascularization in rats.

The association between the use of statins and age-related macular degeneration (AMD), a leading cause of blindness, has been evaluated in many clinical studies; however, the results have been contradictory. We evaluated the effect of pitavastatin administration on laser-induced experimental choroidal neovascularization (CNV) in rats. Brown Norway rats received pitavastatin (1.0mg/kg per day) for 1day prior to laser-induced CNV and continued to receive the drug for 14days. Fluorescein angiograms were graded by masked observers. CNV area and thickness were assessed by fluorescein isothiocyanate-labeled dextran angiography and histology, respectively. Vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (Ccl-2; also known as MCP-1), and intercellular adhesion molecule-1 (ICAM-1) mRNA levels were measured using reverse-transcription polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR. Pitavastatin-treated rats had significantly less fluorescence leakage compared with the vehicle-treated rats estimated by CNV score using fluorescein angiography. Both the area and the thickness of CNV in pitavastatin-treated rats were significantly reduced compared with the vehicle-treated rats. Gene expression of VEGF, Ccl-2, and ICAM-1 were significantly decreased by pitavastatin administration in experimental CNV. Thus, we demonstrated that the therapeutic dose of pitavastatin for human hypocholesterolemia effectively suppressed experimental CNV in rats. The use of pitavastatin may be helpful in preventing CNV development in AMD patients.

Posterior vitreous detachment induced by nattokinase (subtilisin NAT): a novel enzyme for pharmacologic vitreolysis.

PURPOSE: To investigate the effects of intravitreal injection of nattokinase (subtilisin NAT), a serine protease that is produced by Bacillus subtilis (natto), for induction of posterior vitreous detachment (PVD). METHODS: Different doses of nattokinase (1, 0.1, or 0.01 fibrin-degradation units [FU]) or physiologic saline as a control were injected into the vitreous cavity of rabbit eyes. Scanning electron microscopy was used to observe the retinal surfaces of four rabbit eyes per concentration. Histologic alterations were assessed by light microscopy, using four eyes from each group. Electroretinography (ERG) was performed to observe retinal function, ranging from 1 hour to 1 week after the nattokinase (1 or 0.1 FU) or saline solution administration, using four eyes from each group at each time point. Also, findings in all rabbits were monitored by slit lamp examination and by indirect ophthalmoscopy with a 20-D lens. RESULTS: Scanning electron microscopy showed smooth retinal surfaces, indicating the occurrence of PVD at 30 minutes after intervention in all the experimental eyes injected with 0.1 or 1.0 FU nattokinase, but none of the control eyes. Light microscopy and ERG analysis showed no critical change even after the use of 0.1 FU nattokinase, an amount sufficient to induce PVD. However, toxicity in the forms of preretinal hemorrhage and ERG changes was noted with the higher dose (1 FU) of nattokinase. CONCLUSIONS: The results suggested that nattokinase is a useful enzyme for pharmacologic vitreolysis because of its efficacy in inducing PVD.

Intravitreal plasmin injection activates endogenous matrix metalloproteinase-2 in rabbit and human vitreous.

PURPOSE: To investigate the effect of exogenous plasmin administration on the activity of endogenous matrix metalloproteinase-2 (MMP-2) in rabbit and human vitreous. DESIGN: Experimental animal study and interventional case series. METHODS: Human plasmin was injected into rabbit eyes. The active/pro-MMP-2 ratio in vitreous samples was calculated using the gelatin zymography. Scanning electron microscopy (SEM) was performed to observe the retinal surface. To evaluate the time course of MMP-2 activity, vitreous samples were collected after the injection of 0.5 IU of plasmin, and the active/pro-MMP-2 ratio was calculated in the same manner. Immunohistochemical analysis was performed to confirm the presence of MT1-MMP in the rabbit eye. Human vitreous samples obtained from vitreous surgeries were also used for similar studies. RESULTS: The active/pro-MMP-2 ratios in the vitreous after the injection of 0.25 IU or 0.5 IU of plasmin were significantly higher than that of the control (P < .05). SEM demonstrated that plasmin-treated eyes showed a smooth retinal surface that was dose-dependent. Time course evaluation of the active/pro-MMP-2 ratio in the vitreous after the administration of 0.5 IU of plasmin found a significant difference between the 5 and 15 minutes data points compared with that seen for the control. Immunohistochemical study revealed the presence of MT1-MMP in the inner retina. In human samples, the active/pro-MMP-2 ratio after the plasmin injection was significantly higher than the ratio observed before injection. CONCLUSIONS: Our results suggested that activation of endogenous MMP-2 by exogenous plasmin is associated with the induction of posterior vitreous detachment.

Trans-tenon retrobulbar triamcinolone injection for macular edema associated with branch retinal vein occlusion remaining after vitrectomy.

PURPOSE: To evaluate the effectiveness and safety of trans-Tenon retrobulbar triamcinolone injection for macular edema associated with branch retinal vein occlusion (BRVO) after vitrectomy. DESIGN: Prospective interventional case series. METHODS: The study included 20 eyes of 20 patients with BRVO, characterized by macular edema lasting more than 3 months after vitrectomy. Trans-Tenon retrobulbar injection of 40 mg triamcinolone was performed, and visual and anatomic responses were evaluated. RESULTS: Mean foveal thickness was 499.4 +/- 209.1 microm preoperatively, 281.8 +/- 110.1 microm at 2-week follow-up, and 196.9 +/- 92.1 microm at 6-month follow-up (P < .0001, at 2 weeks and 6 months, paired t test). Improvement of visual acuity by at least 0.2 logMAR (logarithm of the minimum angle of resolution) was seen in 14 (70%) of the 20 eyes. CONCLUSIONS: Trans-Tenon retrobulbar injection of triamcinolone may be an alternative for additional treatment of eyes with BRVO that remains after vitrectomy.

Transthyretin synthesis in rabbit ciliary pigment epithelium.

Ocular symptoms of transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP) suggest that ciliary pigment epithelium (CPE) may synthesize TTR and its TTR may lead to amyloid formation in addition to TTR from vessels and retinal pigment epithelium (RPE). To clarify sites of TTR synthesis in ocular tissues, we performed in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR) for qualitative detection of TTR mRNA. In addition, we quantified levels of TTR mRNA expression by means of real-time quantitative RT-PCR. Furthermore, although TTR is an anti-acute phase protein in serum level, no reports on changes in TTR expression in ocular tissues during acute inflammation exist. To investigate changes in TTR expression in ocular tissues during inflammation, we induced uveitis by endotoxin challenge in rabbits and used real-time quantitative RT-PCR to examine changes in TTR mRNA expression in ocular tissues. In situ hybridization and RT-PCR qualitatively demonstrated TTR mRNA not only in RPE but also in CPE. Real-time quantitative RT-PCR showed that the level of TTR mRNA expression in the CPE was about one-third of that in the RPE. TTR mRNA expression in ocular tissues decreased as the degree of inflammation increased. These results suggest that TTR synthesized in the CPE may lead to ocular manifestations, especially glaucoma, in FAP. TTR mRNA also acts as an anti-acute phase reactant in ocular tissues.