LONG-TERM OUTCOMES OF RANIBIZUMAB TREATMENT OF MYOPIC CHOROIDAL NEOVASCULARIZATION IN EAST-ASIAN PATIENTS FROM THE RADIANCE STUDY.

PURPOSE: To evaluate long-term efficacy and safety of ranibizumab for treatment of myopic choroidal neovascularization (mCNV) in clinical practice. METHODS: Noninterventional, retrospective cohort study of East-Asian patients previously treated with ranibizumab during the RADIANCE trial. Forty-one patients who completed the RADIANCE trial were followed-up for up to 48 months (post-RADIANCE observation period). Outcome measures were best-corrected visual acuity changes from baseline (assessed at RADIANCE trial initiation), mCNV recurrences, and ocular adverse events. RESULTS: Mean visual gain from baseline best-corrected visual acuity (56.5 ± 12.1 letters) (20/80) was significant at 12 months (+14.3 ± 11.4 letters, n = 40, P < 0.0001), 24 months (+10.4 ± 22.3 letters, n = 31, P = 0.0143), 30 months (+11.0 ± 22.4 letters, n = 29, P = 0.0134), 42 months (+12.9 ± 20.9 letters, n = 25, P = 0.0051), and 48 months (+16.3 ± 18.7, n = 16, P = 0.0034). Of the 16 patients who completed 48 months of follow-up, 63% gained ≥10 letters and 13% lost ≥10 letters. Over the post-RADIANCE observation period, 83% of patients required no further treatment for mCNV, 10% experienced mCNV recurrences, and 12% experienced a nonserious ocular adverse event. Patients who required additional treatment for mCNV received a mean of 5.0 (SD 5.9, range 1.0-18.0) ranibizumab injections. CONCLUSION: Best-corrected visual acuity gained at the end of the RADIANCE trial was sustained over additional 36 months of follow-up. Few patients required further treatment and no new safety concerns were observed.

SURGICAL OUTCOME OF SIMULTANEOUS INTRAOCULAR LENS RESCUE AND SUTURELESS INTRASCLERAL TUNNEL FIXATION OF DISLOCATED INTRAOCULAR LENSES.

PURPOSE: To report short-term surgical outcomes of single-stage simultaneous rescue and sutureless intrascleral fixation of dislocated intraocular lens (IOLs). METHODS: Sixteen eyes of 16 patients who underwent simultaneous rescue and intrascleral fixation of dislocated 3-piece IOLs were retrospectively evaluated. Partial thickness limbal-based scleral flaps (2.0 × 2.0 mm) were created, and a 22-gauge round needle was used to create a sclerotomy at 1.5 mm from the limbus under the previously created scleral flap, and a 23-gauge trans pars plana vitrectomy was performed. Bimanual maneuvers using two 23-gauge end-grasping forceps under chandelier illumination and a wide-angle viewing system enabled 1 step rescue of IOLs from the posterior vitreous cavity with 1 hand and simultaneous haptic externalization through sclerotomy with the other hand. An externalized haptic was placed into the 3-mm intrascleral tunnel created using a bent 26-gauge needle. Fibrin glue was used to fixate haptics and close the scleral flaps. RESULTS: Intraocular lenses were successfully rescued and sclera-fixated through intrascleral tunnels in all 16 eyes (mean age, 56.56 ± 19.89 years). The mean preoperative logarithm of the minimum angle of resolution best-corrected visual acuity was 0.92 ± 0.68, and this significantly improved at 6 months to 0.289 ± 0.36 (P = 0.003). During the follow-up period (10.1 ± 3.21 months), no significant change of endothelial cell count or central foveal thickness was noted postoperatively (P = 0.203 and P = 0.979, respectively). There were no significant postoperative complications such as IOL dislocation, IOL decentration, retinal detachment, endophthalmitis, or postoperative hypotony. CONCLUSION: Simultaneous rescue and sutureless intrascleral haptic fixation of dislocated 3-piece IOLs using bimanual maneuvers is an effective, safe, and minimally invasive surgical method to rescue and fixate the dislocated IOL without further explant.

Melanocytoma of the optic disk in the Korean population.

PURPOSE: To report on the clinical features and the natural course of optic disk melanocytoma in the Korean population. METHODS: A retrospective review of medical records was performed on 27 consecutive patients with optic disk melanocytoma. In cases with tumor enlargement, surface area and diameter of tumors were measured from fundus images using computer software. RESULTS: The median age at diagnosis was 46 years with a slight female predominance (63%). The median tumor diameter and height were 3.1 mm and 1.9 mm, respectively. There were no cases with tumor-related visual loss for a median follow-up of 2 years. Tumor enlargement was observed in 4 of 21 patients (19%) that had follow-up of 1 year or more with no malignant transformation. The mean change of tumor surface area was 2.4 mm (52% increase), and the mean change of tumor diameter was 1.8 mm over a mean follow-up of 53 months in 4 cases with tumor growth. Only tumor vascularization on fluorescent angiography correlated with tumor growth (Log-rank test; P = 0.049). Kaplan-Meier survival estimated that the tumor growth was 0% at 1 year, 14% at 5 years, and 57% at 8 years. CONCLUSION: Optic disk melanocytoma in the Korean population tends to be superiorly located in the optic disk, and visual prognosis was excellent. Periodic ocular examination is warranted because 57% of patients were estimated to show tumor enlargement by 8 years of follow-up.

Comparison of refractive error in phacovitrectomy for epiretinal membrane using ultrasound and partial coherence interferometry.

PURPOSE: To compare the postoperative refractive error (RE) using A-scan ultrasound (US) and partial coherence interferometry (PCI) after phacovitrectomy for idiopathic epiretinal membrane (iERM) and cataract. METHODS: Eighty-eight participants (88 eyes) with iERM and cataracts underwent phacovitrectomies with internal limiting membrane removal. Postoperative RE was the main outcome measured, calculated by subtracting intended spherical equivalent (SE) from 6-month postoperative SE. Secondary outcomes included axial length (AL) measured by 2 methods, change in best-corrected visual acuity (BCVA), and change in central subfield thickness (CSFT). RESULTS: Mean postoperative RE using US showed greater myopic shift compared with that using PCI (-0.569 ± 0.571 D vs -0.169 ± 0.415 D, respectively, p<0.001). The 6-month postoperative RE was within ±0.50 D in 43.2% (38/88) using US vs 84.1% (74/88) using PCI and within ±1.00 D in 84.1% (74/88) using US vs 96.6% (85/88) using PCI. Mean AL measured by US was shorter than that measured by PCI (23.50 ± 1.27 mm vs 23.58 ± 1.30 mm, respectively, p<0.001). Postsurgery, BCVA improved from 0.374 ± 0.264 logMAR to 0.144 ± 0.124 logMAR (p<0.001), and CSFT decreased from 449.2 ± 78.5 µm to 378.2 ± 47.0 µm (p<0.001). The BCVA improvement significantly correlated with decreased CSFT (R = 0.268, p = 0.011). CONCLUSIONS: Estimation of intraocular lens power for phacovitrectomies for iERM and cataracts is more accurate when assessed by PCI than by US.

Retinal toxicity of commercial tissue plasminogen activator is mediated by the induction of nitric oxide in the mouse retinal primary cells.

PURPOSE: Tissue plasminogen activator (tPA) is an efficient thrombolytic agent, but the dose-dependent retinal toxicity of intravitreal injection of commercial tPA (containing L-arginine) has been reported. Here, we sought to investigate the mechanism of tPA-induced cell death in mouse retinal cell cultures and the role of nitric oxide (NO). METHODS: Primary retinal cell cultures were maintained using glial conditioned medium (GCM) solution. Mouse retinal cell death was observed by using Hoechst-propidium iodide staining. Mouse retinal cell death was also measured by lactate dehydrogenase (LDH) assay. The formation of NO was measured using Griess reagent. RESULTS: tPA-induced cell death was detected in mouse retinal cell cultures by Hoechst-propidium iodide staining or LDH assay. L-arginine seems to be the major factor in retinal toxicity of commercial tPA (containing L-arginine). The formation of NO was markedly increased in mouse retinal cell cultures treated with tPA (containing L-arginine) or L-arginine. NO inhibitor reduced the cell death induced by commercially available tPA or L-arginine. CONCLUSIONS: This study suggests that l-arginine from commercial tPA (containing L-arginine) induces the majority of cell death in mouse retinal cell cultures and that its cytotoxicity may depend on the induction of NO.

Inhibition of choroidal neovascularization in rats by the urokinase-derived peptide A6.

PURPOSE: To evaluate the inhibitory effects of a urokinase-derived octapeptide A6 on laser-induced choroidal neovascularization (CNV). METHODS: In the first arm of the study, subcutaneous injection of A6 (200 mg/kg per day) into the right eyes in 20 rats and phosphate-buffered saline in 20 control rats was started 1 day before laser injury. Angiography was performed at week 2. To evaluate the dose response, a second arm of the study was performed in the left eyes. Half of the treatment group was treated with 400 mg/kg per day, and the remaining half continued to receive 200 mg/kg per day beginning on week 4. Laser injury was made at week 5 and angiography was performed at week 7. Angiographic evaluation, histopathologic evaluation including maximum CNV thickness and factor-VIII-stained endothelium counting were performed in the second arm of the study. Choroidal concentrations of A6 were measured. RESULTS: In the first arm of the study, angiography showed a 40.8% reduction in CNV in the 200-mg/kg per day treatment group, compared with the control (P = 0.0008). In the second arm of the study, angiographic reduction in CNV was 37.9% in the 200-mg/kg per day group (P = 0.0314) and 70.0% in the 400-mg/kg per day group (P = 0.0124), compared with the control. CNV was significantly less in the 400-mg/kg per day group than in the 200-mg/kg per day group (P = 0.0393). Both CNV thickness and number of endothelial cells were reduced in a dose-dependent manner and significantly less than in the control (P < 0.05). Mean choroidal concentration of A6 2 hours after injection was 0.72 micro M in the 200-mg/kg per day (100 mg/kg every 12 hours) and 1.75 micro M in the 400-mg/kg per day (200 mg/kg every 12 hours) treatment groups. Levels at 11 hours after injections were undetectable. CONCLUSIONS: A6 demonstrated antiangiogenic properties in a rat model of CNV and may be useful in the treatment of CNV.

Visual field defect caused by nerve fiber layer damage associated with an internal limiting lamina defect after uneventful epiretinal membrane surgery.

PURPOSE: To report a case of visual field defect caused by damage of the nerve fiber layer associated with an internal limiting lamina defect after uneventful epiretinal membrane peeling. DESIGN: Interventional case report. METHODS: In the right eye, a 43-year-old male patient developed a nasal step and mild inferior arcuate scotoma after uneventful epiretinal membrane surgery without any associated glaucoma. Transmission electron microscopy was performed on the epiretinal membrane specimens. RESULTS: An epiretinal membrane specimen showed adhesion between epiretinal membrane and axons of nerve fiber layer in the area of the internal limiting lamina defect. CONCLUSION: Adhesion between epiretinal membrane and retinal tissue in the area of the internal limiting lamina defect may cause damage of the nerve fiber layer and visual field defect after epiretinal membrane peeling.

Photodynamic therapy using verteporfin-induced minimal change nephrotic syndrome.

PURPOSE: To report a case of minimal change nephrotic syndrome (MCNS) after photodynamic therapy using verteporfin. DESIGN: Interventional case report. METHODS: After four cycles of photodynamic therapy, general weakness with generalized edema developed in an otherwise healthy 66-year-old woman, resulting in dyspnea and ascites. Urinalysis showed heavy proteinuria (4+) with decreased serum total protein and albumin, and increased total cholesterol levels, suggesting nephrotic syndrome. Renal biopsy and pathologic diagnosis were performed. RESULTS: Renal biopsy revealed normal glomeruli and tubulointerstitium by light microscopy, with no immunoglobin or complement deposition. Transmission electron microscopy showed diffuse effacement of the foot processes of visceral epithelial cells, which is the characteristic finding of minimal change nephrotic syndrome. CONCLUSIONS: We herein report a case of minimal change nephrotic syndrome after photodynamic therapy using verteporfin.

Valganciclovir therapy for immune recovery uveitis complicated by macular edema.

PURPOSE: To determine whether treatment with valganciclovir will improve visual acuity in eyes with immune recovery uveitis complicated by macular edema. DESIGN: Prospective open label controlled Phase II drug study. METHODS: Five patients with chronic macular edema as a result of immune recovery uveitis were studied. Baseline fluorescein angiograms, best-corrected ETDRS visions, and cytomegalovirus (CMV) lymphoproliferative T-cell function assays were obtained and repeated after three months of valganciclovir therapy (900 mg daily) and again three months after withdrawal of therapy. RESULTS: Vision improved by a mean of 11 letters in the treatment phase (P =.05). Graded angiograms showed three patients had treatment reduction of macular edema. One patient had rebound increase in macular edema after the withdrawal phase. The CMV lymphoproliferative response was not affected by the valganciclovir. CONCLUSION: Results suggest valganciclovir treatment may benefit visual acuity in patients with macular edema from immune recovery uveitis.

Iris synechia after laser goniopuncture in a patient having deep sclerectomy with a collagen implant.

Neodymium:YAG (Nd:YAG) goniopuncture is an efficient and safe treatment for low filtration through the trabeculo-Descemet's membrane after deep sclerectomy with a collagen implant (DSCI). The only reported complication of this procedure is choroidal detachment. However, we found an iris synechia in a patient whose intraocular pressure (IOP) was elevated again 1 month after Nd:YAG goniopuncture. Synechiolysis and peripheral iridectomy with Nd:YAG and argon lasers effectively removed the iris synechia, and IOP immediately dropped to the normal range. We believe that iris synechia is a potential complication that may cause elevated IOP after laser goniopuncture in patients having DSCI.

Opacification of a hydrophilic acrylic intraocular lens with exacerbation of Behçet's uveitis.

Behçet's disease is 1 of the most common causes of uveitis in the Eastern world. Its common ocular complications are uveitis, cataract, and obliteration of retinal vessels. Phacoemulsification with intraocular lens (IOL) implantation in patients with Behçet's disease is known to be a safe procedure. We managed a patient with Behçet's disease who had aggravated uveitis and opacification of a hydrophilic acrylic IOL (ACRL-C160, Ophthalmed) 4 months after cataract surgery. Recalcitrant uveitis despite maximum tolerable medication and IOL opacification with vitreous opacity necessitated an IOL exchange and trans pars plana vitrectomy. After the procedure, the eye became quiescent. However, the visual acuity was 20/200 because of the obliteration of retinal vessels.

Intraocular properties of urokinase-derived antiangiogenic A6 peptide in rabbits.

To investigate the intraocular properties of an antiangiogenic peptide, A6, a total of 70 New Zealand rabbit eyes were used. For the toxicity study, 0.05 mL of 0.459 M or 0.148 M A6 was injected intravitreally; right eyes received A6, and left eyes received a vehicle. Serial intraocular pressure measurement, slit lamp, and indirect ophthalmoscopy were performed. The rabbit eyes were evaluated by fluorescein angiography, electroretinography, and histology after the scheduled sacrifice. The pharmacokinetics of an intravitreal A6 (0.05 mL of 0.488 M) and a subtenon A6 (0.5 mL of 0.305 M) injection was studied. There was no toxicity observed following the 0.148 M A6 intravitreal injections. In 2 eyes with a 0.459 M A6 intravitreal injection, focal retinal pigmentary change was observed at the injection site, which was contacted by the hyperosmolar drug bolus. Choroidal A6, following the intravitreal injection, remained therapeutic (>or=10 microM) for 72 hours. The vitreous half-life was 19.4 hours. Choroidal concentrations following the subtenon injection were minimal. The low choroidal concentrations observed may relate to the polar nature of A6. More hydrophobic analogs of A6 are likely to cross the retina more efficiently. However, in diseased eyes, in the area of choroidal neovascularization (CNV), the fluid-filled, damaged, edematous retina may permit the drug to enter the choroid in higher concentrations.

Prognostic factors in vitrectomy for lamellar macular hole assessed by spectral-domain optical coherence tomography.

PURPOSE: To evaluate the association between the macular structure on spectral-domain optical coherence tomography (SD-CT) and visual outcome after vitrectomy for lamellar macular hole (LMH). METHODS: Best-corrected visual acuity (VA) and SD-OCT images of the macula were assessed before and after surgery in 30 eyes of 30 patients with a LMH. Preoperative VA and SD-OCT features were investigated as predictors of surgical outcome. RESULTS: Mean patient age was 65 years with female predominance (77%). Visual acuity improved in 19 eyes (63%) with an overall mean improvement of 1 Snellen line (from 20/65 to 20/50; p = 0.002) at a mean of 18 months after vitrectomy. Subgroup analysis showed that statistically significant visual benefit was only observed in patients with an intact photoreceptor inner segment/outer segment (IS/OS) junction (p = 0.003), with foveal thickness bigger than 100 µm (p = 0.004) and with initial VA better than 20/100 (p = 0.003). The most efficient model to predict final VA was the combination of preoperative VA and the presence or absence of IS/OS disruption (r(2) = 0.77, p < 0.001). CONCLUSIONS: Poor initial VA, the presence of a disrupted IS/OS junction or a thin fovea on preoperative SD-OCT predicted poor vision outcome after LMH surgery.

Prophylactic intraoperative 360 degrees laser retinopexy for prevention of retinal detachment.

PURPOSE: To evaluate the effect of intraoperative 360 degrees laser retinopexy anterior to the equator for the prevention of retinal detachment after vitrectomy. DESIGN: Retrospective comparative consecutive case-control study. PARTICIPANTS: A consecutive case series of 220 patients with vitreal or macular diseases excluding retinal detachment who underwent vitrectomy by a single surgeon (W.R.F.) in a teaching situation between July 1999 and January 2003. A consecutive cohort of patients who had undergone 360 degrees laser retinopexy was identified (n=115) and compared with a control group of patients who had not received laser retinopexy (n=105). For the 360 degrees laser treatment group, three rows of medium-white burns were placed anterior to the equator. METHODS: Demographic and clinical data were extracted from patients' medical records. The baseline characteristics and the risk of retinal detachment over time were analyzed and compared between the 360 degrees laser treatment group and the control group. MAIN OUTCOME MEASURE: Occurrence of retinal detachment after vitrectomy. RESULTS: There was no significant difference in baseline characteristics between the two consecutive series (the 360 degrees laser treatment group and the control group). Intraoperative 360 degrees laser retinopexy was associated with a threefold reduction in the incidence of retinal detachment after surgery from 13.3% to 3.5% (Kaplan-Meier analysis log-rank test, P=0.0225; Cox proportional hazards regression, P=0.0321). CONCLUSIONS: Intraoperative 360 degrees laser retinopexy following vitrectomy showed an encouraging reduction (approximately 74%) in the rate of postoperative retinal detachment without any apparent adverse effects. Considering the vision-threatening nature of retinal detachment, this adjunctive treatment should be considered to be used in vitrectomy procedures.

Intravitreal toxicity of the kenalog vehicle (benzyl alcohol) in rabbits.

PURPOSE: To test the toxicity of intravitreal injections of benzyl alcohol. METHODS: Nine New Zealand rabbits were injected with either a control or a test article at elevating concentrations. The test article was benzyl alcohol calculated to give final injected concentrations of 0.0073%, 0.022%, 0.073%, 0.222%, and 0.733% benzyl alcohol. The 0.022% concentration corresponds to the concentration of benzyl alcohol in human eyes when 0.1 mL of commercial Kenalog (Bristol-Myers Squibb, Princeton, NJ) is used. Baseline examination of the rabbits was performed along with postinjection examinations on days 1, 3, 7, and 14. The eyes were enucleated and examined by light and electron microscopic examinations. RESULTS: Eyes injected with benzyl alcohol concentrations of 0.073%, 0.222%, and 0.733% displayed changes in the outer retina including loss of, and shortening of, outer segments and photoreceptors. CONCLUSIONS: Benzyl alcohol at concentrations modestly higher than what is present in commercial Kenalog is toxic to the rabbit eye. This has been shown in other organ systems. If commercial preserved Kenalog is to be used clinically, decanting the supernatant or using other means to remove the benzyl alcohol may be considered, especially if a volume of >0.1 mL of solution is used. We hypothesize that the noninfectious inflammation seen clinically after Kenalog injection is due to the presence of a toxic preservative at unsafe concentrations.

Effect of a novel octapeptide urokinase fragment, A6, on experimental choroidal neovascularization in the monkey.

PURPOSE: To evaluate the inhibitory effects of a urokinase-derived octapeptide, A 6, on laser-induced choroidal neovascularization (CNV) in monkeys. METHODS: Twenty female cynomolgus monkeys were randomly grouped into weekly or monthly A 6 treatment groups, each consisting of 10 animals. CNV was induced in both eyes by perimacular laser treatment. In each right eye, a single 22.25-mg A 6 dose (monthly group) or 4 22.25-mg A 6 doses each week (weekly group) were given by intravitreal injections. Each left eye received phosphate buffer on the same schedule. Monkeys were observed for 4 weeks by ophthalmic examinations, color photography, and fluorescein angiography. RESULTS: Weekly treated eyes had a 35% reduction of CNV compared with controls (P = 0.23). In contrast, monthly treated eye had a 71% reduction of CNV compared with controls (P = 0.0009). There was no evidence of toxicity at both clinical and pathologic examinations. CONCLUSIONS: Intravitreal A 6 injections effectively inhibited CNV in cynomolgus monkeys without evidence of toxicity. The overall reduction in CNV was greater for monthly treated eyes than for weekly treated eyes. This study suggests that A 6 has promise as a local antiangiogenic treatment of CNV. Further work is indicated to evaluate the potential role of A 6 in therapy for human CNV associated with age-related macular degeneration.

The effect of photodynamic therapy with rose bengal on posterior capsule opacification in rabbit eyes.

We investigated the in vivo effect of photodynamic therapy (PDT) using rose bengal on the development of posterior capsule opacification (PCO). Endocapsular phacoemulsification was performed on white rabbits, which were divided into 4 groups: control group; group 1, treated with visible light only; group 2, treated with rose bengal only, and group 3, treated with PDT. In the case of the PDT group, rose bengal dissolved in sodium hyaluronate was injected into the empty capsular bag and treated with visible light. Three months after surgery, the rabbits were sacrificed and the eyeballs enucleated. The obstruction rate of visible light caused by PCO was measured with an optical powermeter. The mean obstruction rate was 30.6% in the control group, 28.3% in group 1, 19.3% in group 2, and 14.3% in group 3. Group 3 showed a statistically significant decrease in PCO compared with the control group and group 1 (p = 0.0014). Our results suggest that PDT using rose bengal effectively decreased PCO in rabbit eyes.