Screening Medications for Association with Progression to Wet Age-Related Macular Degeneration.

PURPOSE: There is an urgent need for treatments that prevent or delay development to advanced age-related macular degeneration (AMD). Drugs already on the market for other conditions could affect progression to neovascular AMD (nAMD). If identified, these drugs could provide insights for drug development targets. The objective of this study was to use a novel data mining method that can simultaneously evaluate thousands of correlated hypotheses, while adjusting for multiple testing, to screen for associations between drugs and delayed progression to nAMD. DESIGN: We applied a nested case-control study to administrative insurance claims data to identify cases with nAMD and risk-set sampled controls that were 1:4 variable ratio matched on age, gender, and recent healthcare use. PARTICIPANTS: The study population included cases with nAMD and risk set matched controls. METHODS: We used a tree-based scanning method to evaluate associations between hierarchical classifications of drugs that patients were exposed to within 6 months, 7 to 24 months, or ever before their index date. The index date was the date of first nAMD diagnosis in cases. Risk-set sampled controls were assigned the same index date as the case to which they were matched. The study was implemented using Medicare data from New Jersey and Pennsylvania, and national data from IBM MarketScan Research Database. We set an a priori threshold for statistical alerting at P ≤ 0.01 and focused on associations with large magnitude (relative risks ≥ 2.0). MAIN OUTCOME MEASURES: Progression to nAMD. RESULTS: Of approximately 4000 generic drugs and drug classes evaluated, the method detected 19 distinct drug exposures with statistically significant, large relative risks indicating that cases were less frequently exposed than controls. These included (1) drugs with prior evidence for a causal relationship (e.g., megestrol); (2) drugs without prior evidence for a causal relationship, but potentially worth further exploration (e.g., donepezil, epoetin alfa); (3) drugs with alternative biologic explanations for the association (e.g., sevelamer); and (4) drugs that may have resulted in statistical alerts due to their correlation with drugs that alerted for other reasons. CONCLUSIONS: This exploratory drug-screening study identified several potential targets for follow-up studies to further evaluate and determine if they may prevent or delay progression to advanced AMD.

Incidence of Macular Atrophy after Untreated Neovascular Age-Related Macular Degeneration: Age-Related Eye Disease Study Report 40.

PURPOSE: To report the natural history of untreated neovascular age-related macular degeneration (nAMD) regarding subsequent macular atrophy. DESIGN: Prospective cohort within a randomized, controlled trial of oral micronutrient supplements. PARTICIPANTS: Age-Related Eye Disease Study (AREDS) participants (55-80 years) who demonstrated nAMD during follow-up (1992-2005), prior to anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Color fundus photographs were collected at annual study visits and graded centrally for late age-related macular degeneration (AMD). Incident macular atrophy after nAMD was examined by Kaplan-Meier analysis and proportional hazards regression. MAIN OUTCOME MEASURES: Incident macular atrophy after nAMD. RESULTS: Of the 4757 AREDS participants, 708 eyes (627 participants) demonstrated nAMD during follow-up and were eligible. The cumulative risks of incident macular atrophy after untreated nAMD were 9.6% (standard error, 1.2%), 31.4% (standard error, 2.2%), 43.1% (standard error, 2.6%), and 61.5% (standard error, 4.3%) at 2, 5, 7, and 10 years, respectively. This corresponded to a linear risk of 6.5% per year. The cumulative risk of central involvement was 30.4% (standard error, 3.2%), 43.4% (standard error, 3.8%), and 57.0% (standard error, 4.8%) at first appearance of atrophy, 2 years, and 5 years, respectively. Geographic atrophy (GA) in the fellow eye was associated with increased risk of macular atrophy (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.17-2.49; P = 0.006). However, higher 52-single nucleotide polymorphism AMD genetic risk score was not associated with increased risk of macular atrophy (HR, 1.03; 95% CI, 0.90-1.17; P = 0.67). Similarly, no significant differences were observed according to SNPs at CFH, ARMS2, or C3. CONCLUSIONS: The rate of incident macular atrophy after untreated nAMD is relatively high, increasing linearly over time and affecting half of eyes by 8 years. Hence, factors other than anti-VEGF therapy are involved in atrophy development, including natural progression to GA. Comparison with studies of treated nAMD suggests it may not be necessary to invoke a large effect of anti-VEGF therapy on inciting macular atrophy, although a contribution remains possible. Central involvement is present in one third of eyes at the outset (similar to pure GA) and increases linearly to half at 3 years.

Repeated intravitreal injections of antivascular endothelial growth factor in patients with neovascular age-related macular degeneration may increase the risk of ischemic optic neuropathy.

BACKGROUND: Previous case reports have demonstrated the occurrence of ischemic optic neuropathy (ION) following intravitreal injections of antivascular endothelial growth factor (anti-VEGF). However, no previous studies have investigated the impact of injection numbers on the risk of ION. The aim of our study was to investigate whether repeated intravitreal injections of anti-VEGF would increase the risk of subsequent ION in patients with neovascular age-related macular degeneration (AMD). METHODS: A population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from 2007 to 2013. Neovascular AMD patients receiving intravitreal injections of anti-VEGF during the study period were enrolled in the study cohort. Enrollees were divided into three groups according to the categorized levels of injection number (first level: < 10 times, second level: 10-15 times, and third level: > 15 times). Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent ION among the three groups. Cox regression analyses were used to estimate crude and adjusted hazard ratios (HRs) for ION development with respect to the different levels of injection numbers. The confounders included for adjustment were age, sex, and comorbidities (diabetes, hypertension, hyperlipidemia, ischemic heart disease, and glaucoma). RESULTS: In total, the study cohort included 77,210 patients. Of these, 26,520, 38,010, and 12,680 were in the first-, second-, and third-level groups, respectively. The Kaplan-Meier method revealed that the cumulative hazards of ION were significantly higher in those who had a higher injection number. After adjusting for confounders, the adjusted HRs for ION in the second- and third-level groups were 1.91 (95% confidence interval [CI], 1.32-2.76) and 2.20 (95% CI, 1.42-3.43), respectively, compared with those in the first-level group. CONCLUSIONS: Among patients with neovascular AMD, those who receive a higher number of anti-VEGF injections have a significantly higher risk of developing ION compared with individuals who receive a lower number of injections.

Stereological Method in Optical Coherence Tomography for In Vivo Evaluation of Laser-Induced Choroidal Neovascularization.

BACKGROUND AND OBJECTIVE: To evaluate a stereological method in optical coherence tomography (OCT) as an in vivo volume measurement of laser-induced choroidal neovascularization (L-CNV) lesion size. PATIENTS AND METHODS: Laser photocoagulation was applied in rats to rupture Bruch's membrane and induce L-CNV. In vivo OCT images of neovascular lesions were acquired with a spectral-domain OCT system at days 0, 3, 7, 10, and 14 after laser surgery. A stereological image-processing method was used to calculate lesion volumes from the OCT images. Rats were euthanized at day 14, and confocal microscopy was used to obtain accurate volume measurements of the lesions ex vivo. Lesion sizes calculated from OCT and confocal were compared. RESULTS: In vivo assessment by OCT allowed three distinct stages of L-CNV to be visualized: the initial early reaction, neovascular proliferation, and regression. At day 14, correlations between OCT and confocal lesion volumes showed a positive association (Pearson's r = 0.50, P < .01). Except for the largest lesions, volumes measured by OCT were statistically similar to those measured by the confocal gold standard (P = .90). CONCLUSION: The stereological approach used to measure neovascular lesion volume from OCT images offers an accurate means to track L-CNV lesion size in vivo. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e65-e74.].

Two week, OCT-based follow-up as guidance for retreatment with ranibizumab for CNV apparently refractory to therapy.

PURPOSE: To assess the value of 2-week optical coherence tomography (OCT) follow-up for re-treatment decision-making in patients receiving monthly ranibizumab injections for choroidal neovascular membrane (CNV), which was apparently refractory to treatment. METHODS: A total of 25 eyes of 25 consecutive patients with refractory CNV were included. Patients were classified as having refractory disease if no visual acuity (VA) change and no change in the pattern of macular fluid was noticed on OCT after at least 3 consecutive monthly injections, excluding the loading doses. Repeat injection was given and reassessment with VA and OCT was undertaken at 2, 4, 8, and 12 weeks. RESULTS: Complete resolution or marked reduction of macular fluid was noted in 19 patients at 2 weeks (responders). In 18 responders, the fluid increased on 4- and persisted on 8- and 12-week follow-ups, so that further injections were given at these time points. In 6 patients, no significant change was noted at 2 weeks (nonresponders). In all of them, VA and OCT were stable on 4-, 8-, and 12-week follow-ups, without further injections. CONCLUSIONS: As some patients are responding for at least part of the month, injections may be worth continuing or possibly more frequent injections, tailored to the individual's response, may need to be considered. Alternative therapies such as aflibercept may also need to be considered. In nonresponding eyes, other cytokines except for vascular endothelial growth factor are probably involved in the pathogenesis or such cases may have structural damage that will not respond to therapy.

Intravitreal polypoidal choroidal vasculopathy in radiation retinopathy.

A 30-year-old woman diagnosed with choroidal melanoma and treated with plaque radiation and transpupillary thermotherapy 5 years earlier presented with recalcitrant proliferative radiation retinopathy despite multiple intravitreal anti-vascular endothelial growth factor injections. Swept-source and spectral-domain optical coherence tomography (OCT) demonstrated intravitreal polyps lying on the surface of atrophied chorioretinal tissue. Fluorescein angiography (FA) revealed leakage from these saccular choroidal neovasculopathic vessels adjacent to a large zone of poor choroidal perfusion. Intravitreal polypoidal choroidal vasculopathy may be associated with radiation retinopathy and is well-demonstrated with swept-source and spectral-domain OCT and FA.

Optical coherence tomography and histopathology of macular uveitis.

PURPOSE: Spectral-domain optical coherence tomography (SD-OCT) is a noninvasive technique that can provide high-resolution images of macular morphology. The purpose of this study was to examine the pathological mechanism of uveitis and compare the changes in the macula of uveitis patients and the histopathological features of experimentally induced uveitis in mice. METHODS: Macular OCT was performed on 78 eyes of 51 patients of the Eye Hospital of Shandong University of Traditional Chinese Medicine, China, with apparent uveitis changes. C57BL/6 mice were injected with interphotoreceptor retinoid-binding protein (IRBP)-specific T cells from naïve mice immunized with complete Freund adjuvant IRBP(1-20) to induce uveitis. The disease was monitored by indirect fundoscopy. The eyes of the mice with experimental autoimmune uveitis (EAU) were enucleated 18 days after injection and classified according to pathological characteristics. RESULTS: The characteristics of uveitis were classified into six categories. Macular edema was detected in 48 eyes (61.5%); macular epiretinal membrane in 22 eyes (28.2%); choroidal neovascularization and macular lamellar holes in 4 eyes (5.1%), respectively; macular atrophy in 10 eyes (12.8%); and serous neuroepithelium detachment in 22 eyes (28.2%). As in human patients, pathological examinations of mouse EAU showed inflammation, folds, and atrophy of the outer part of the neuroretina, choroidal neovascularization with hemorrhagic retinal detachment, serous neuroepithelium detachment, and epiretinal membrane formation. CONCLUSIONS: Macular OCT of uveitis patients can display different morphological characteristics. Mouse EAU can simulate human uveitis. The comparative analysis of macular OCT in human uveitis and transfer EAU histopathology changes could provide important information on the pathogenesis of human uveitis.

Suppression of experimental choroidal neovascularization by curcumin in mice.

PURPOSE: To investigate the effects of curcumin on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms. METHODS: C57BL/6N mice were pretreated with intraperitoneal injections of curcumin daily for 3 days prior to laser-induced CNV, and the drug treatments were continued until the end of the study. The CNV area was analyzed by fluorescein-labeled dextran angiography of retinal pigment epithelium (RPE)-choroid flat mounts on day 7 and 14, and CNV leakage was evaluated by fluorescein angiography (FA) on day 14 after laser photocoagulation. The infiltration of F4/80 positive macrophages and GR-1 positive granulocytes were evaluated by immunohistochemistry on RPE-choroid flat mounts on day 3. Their expression in RPE-choroid complex was quantified by real-time PCR (F4/80) and Western blotting (GR-1) on day 3. RPE-choroid levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 were examined by ELISA on day 3. Double immunostaining of F4/80 and VEGF was performed on cryo-sections of CNV lesions on day 3. The expression of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)-1α in the RPE-choroid was determined by Western blotting. RESULTS: Curcumin-treated mice had significantly less CNV area (P<0.05) and CNV leakage (P<0.001) than vehicle-treated mice. Curcumin treatment led to significant inhibition of F4/80 positive macrophages (P<0.05) and GR-1 positive granulocytes infiltration (P<0.05). VEGF mainly expressed in F4/80 positive macrophages in laser injury sites, which was suppressed by curcumin treatment (P<0.01). Curcumin inhibited the RPE-choroid levels of TNF-α (P<0.05), MCP-1 (P<0.05) and ICAM-1 (P<0.05), and suppressed the activation of NF-κB in nuclear extracts (P<0.05) and the activation of HIF-1α (P<0.05). CONCLUSION: Curcumin treatment led to the suppression of CNV development together with inflammatory and angiogenic processes including NF-κB and HIF-1α activation, the up-regulation of inflammatory and angiogenic cytokines, and infiltrating macrophages and granulocytes. This provides molecular and cellular evidence of the validity of curcumin supplementation as a therapeutic strategy for the suppression of age-related macular degeneration (AMD)-associated CNV.

[Pharmacological treatment for retinopathy of prematurity]. / Pharmakologische Therapie der Frühgeborenenretinopathie.

Mandatory screening performed by an experience ophthalmologist remains the most important pillar in the management of retinopathy of prematurity (ROP). The current gold standard for treatment of proliferative ROP is still panretinal laser photocoagulation, depending on severity, in combination with vitreoretinal surgery if necessary. The first case series of off-label intravitreal anti-VEGF treatment are encouraging. In addition to intravitreal anti-VEGF therapy, other treatment concepts such as supplementation with IGF-1 or omega-3 fatty acids also represent interesting pharmacological approaches to the management of ROP. However, larger controlled trials are required to validate the benefits and safety of these systemic treatment approaches.

Transpupillary thermotherapy of subfoveal choroidal neovascularization secondary to pathologic myopia.

BACKGROUND AND OBJECTIVE: To assess the safety and effectiveness of transpupillary thermotherapy treatment of subfoveal choroidal neovascular membrane secondary to pathologic myopia. PATIENTS AND METHODS: Seventy-four patients (74 eyes) with pathologic myopia underwent transpupillary thermotherapy treatment using a 3.0-mm spot size, 1-minute duration, and 520-mW power delivered through a contact lens. Clinical evaluation included measurement of best-corrected Snellen visual acuity, slit-lamp biomicroscopy, fundus color photography, and fluorescein angiography. RESULTS: Sixty-four eyes (86%) received one treatment session. Six eyes (8%) improved 0.1 logarithm of the minimum angle of resolution (LogMAR) visual acuity post-treatment, 10 eyes (13.5%) lost more than 0.2 LogMAR acuity, and another 10 eyes (13.5%) lost 0.1 LogMAR acuity. The remaining 48 eyes (65%) had unchanged visual acuity after the last follow-up visit. CONCLUSION: Transpupillary thermotherapy preserves vision in patients with choroidal neovascular membrane associated with pathologic myopia. Younger patients and eyes with higher refractive error are more likely to benefit from treatment.

Inflammatory choroidal neovascular membrane in posterior uveitis-pathogenesis and treatment.

Choroidal neovascular membrane (CNVM) formation is a well-documented sight-threatening complication of posterior segment intraocular inflammation (PSII). The aim of this article is to review the basic and clinical science literature on the pathogenesis of CNVM formation in PSII and to present results of a case series. We searched the literature using the mesh terms- inflammation, CNVM, age-related macular degeneration, immunosuppression, photodynamic therapy, steroids, vascular endothelial growth factors and posterior uveitis. Additionally, we evaluated the visual outcome of and clinical response to our standard treatment protocol involving a combination treatment for young patients with inflammatory CNVM. The development of CNVM in PSII is promulgated by infiltrating myeloid cells as well as choroidal and retinal myeloid cell activation, subsequent vascular endothelial growth factors, cytokine and chemokine production and complement activation acting in consort to mediate angiogenic responses. No clear standard of care currently exists for the treatment of inflammatory CNVM and various combinations have been tried. Using our combination treatment, visual acuity improved in four, stabilized in one and worsened in four patients. Though significant advances have occurred in the understanding of the pathogenesis and management of this condition, optimizing therapeutic regimens will require further well-constructed prospective cohort series.

Non-arteritic anterior ischemic optic neuropathy (NA-AION) after intravitreal injection of bevacizumab (Avastin) for treatment of angoid streaks in pseudoxanthoma elasticum.

BACKGROUND: To report a case of nonarteritic anterior ischemic optic neuropathy (NA-AION) following intravitreal injection of bevacizumab (Avastin). METHODS: Interventional case report with an 18-month follow-up. RESULTS: A 51-year-old male with pseudoxanthoma elasticum presented with NA-AION 2 weeks after treatment with intravitreal of bevazicumab (Avastin) for choroidal neovascularisation secondary to angioid streaks. Except from a small optic disc without cupping he did not show further risk factors. DISCUSSION: Risk of NA-AION should be taken into consideration when deciding for intravitreal application of drugs including anti-vascular endothelial growth factors (VEGF) agents like bevacizumab (Avastin) in the treatment of retinal vascular diseases.

Preclinical evaluation of the novel small-molecule integrin alpha5beta1 inhibitor JSM6427 in monkey and rabbit models of choroidal neovascularization.

OBJECTIVE: To evaluate the pharmacologic activity and tolerability of JSM6427, a potent and first selective small-molecule inhibitor of integrin alpha5beta1, in monkey and rabbit models of choroidal neovascularization (CNV). METHODS: JSM6427 selectivity for alpha5beta1 was evaluated by in vitro binding assays while the ability of JSM6427 to inhibit CNV was investigated in a laser-induced monkey model and a growth factor-induced rabbit model. Intravitreal injections of JSM6427 (100, 300, or 1000 microg) or vehicle were administered immediately after the CNV induction procedure and at weekly intervals for 4 weeks. Fluorescein angiography was performed weekly. Ocular tolerability was evaluated ophthalmoscopically and histologically in both models; additional assessments in monkeys included electroretinography, biomicroscopy, pathological examination, and analysis of JSM6427 pharmacokinetics. RESULTS: JSM6427 was highly selective for the alpha5beta1-fibronectin interaction. Weekly intravitreal injections of JSM6427 resulted in a statistically significant dose-dependent inhibition of CNV in laser-induced and growth factor-induced models without any ocular JSM6427-related adverse effects. JSM6427 was cleared through the systemic circulation with no evidence of systemic accumulation. CONCLUSIONS: Intravitreal JSM6427 provided dose-dependent inhibition of CNV in monkey and rabbit experimental models. CLINICAL RELEVANCE: JSM6427 may provide a new approach for the treatment of ocular neovascular diseases such as age-related macular degeneration in humans.

[Basic principles and clinical application of retinal laser therapy]. / Grundlagen und klinische Anwendung der Lasertherapie an der Netzhaut.

The scientific background of laser photocoagulation of the ocular fundus was studied extensively by several investigators in the 1970 s and 1980 s. The basic principles were successfully resolved during that time and clinical consequences for proper application of the laser photocoagulation for various diseases were deduced. The present paper gives an overview about the physical basics of laser-tissue interactions during and after retinal laser treatment and the particular laser strategies in the treatment of different retinal diseases. Thus, it addresses the issue of the impact on tissue of laser parameters as wavelength, spot size, pulse duration and laser power. Additionally, the different biological tissue reactions after laser treatment are presented, such as, e. g., for retinopexia or macular treatments as well as for diabetic retinopathies. Specific laser strategies such as the selective laser treatment of the RPE (SRT) or the transpupillary thermotherapy (TTT) are presented and discussed.

Combination of photodynamic therapy with intravitreal bevacizumab for post-peribulbar anesthesia (penetrating trauma)-persistent choroidal neovascular membrane.

We report a case of a choroidal neovascular membrane (CNVM) following ocular penetration during peribulbar anesthesia in a 55-year-old male patient. A combination of photodynamic therapy with intravitreal bevacizumab led to resolution of the persistent CNVM.

Macular microcirculation blood flow in patients with age related macular degeneration treated with photodynamic therapy and transpupillary thermotherapy.

PURPOSE: To assess the macular retinal and choroidal microcirculation blood flow in patients with exudative age related macular degeneration before and after photodynamic therapy (PDT) or transpupillary thermotherapy (TTT) with Doppler laser scanning (HRF--Heidelberg retinal flowmeter). MATERIAL AND METHODS: Thirty patients with exudative age-related macular degeneration were included in a prospective study. The diagnosis was established based on ophthalmic examination and fluorescein angiography results. In all cases the subfoveal choroidal neovascularization (CNV) was present. Control group consists of the fellow eyes with early stage of AMD (19 eyes) or with disciform scar (11 eyes). In 15 eyes with active CNV PDT was performed and in remaining 15--TTT. In all cases the macular blood flow was measured with Heidelberg retina flowmeter (HRF) before therapy and then 1 week, 4 weeks and 10-12 weeks after treatment. RESULTS: At the baseline examination in a group of eyes with active CNV the mean values of macular blood flow were significantly higher comparing to the fellow eyes and reached respectively: 678.6 +/- 125.0 AU and 298.4 +/- 79.2 AU (p=0.001). Four weeks after treatment all eyes showed the reduction of macular blood flow comparing to the baseline values (p=0.001). Ten to twelve weeks after laser therapy in all cases the increased macular blood flow was detected comparing to the previous examination (p=0.01). During the follow-up period the macular blood flow in the fellow eyes were significantly lower than in treated eyes. CONCLUSIONS: The measurement of macular blood flow using Doppler scanning laser (HRF--Heidelberg retinal flowmeter) may act as a non-invasive and useful diagnostic tool in assessment of CNV activity in patients with exudative age-related degeneration before and after PDT or TTT.

[Complex diagnosis of the early macular changes due to AMD]. / Kompleksowa diagnostyka wczesnych zmian w plamce w przebiegu zwyrodnienia plamki zwiazanego z wiekiem.

We demonstrated diagnostic cases of the early macular changes due to AMD, which caused central visual field disturbances. The aim of the study was to systemize the management in patients with macular lesions due to the age related macular degeneration, frequency determination and statement of the performed additional tests range. Patients reported central visual field distortions. We performed visual acuity testing, stereoscopic eye fundus examination, and PHP (macular visual field testing), which objectified distortions symptoms. Based on that tests and fellow eye condition, decision about OCT and FA and ICG performance were made. Further management was determined according to the results of that examinations: follow-up with vitamins and microelements supplementation or PDT. Our analysis confirm, that to monitor early macular changes due to AMD, follow-up examinations in 2-3 months interval are indicated: visual acuity testing, stereoscopic eye fundus examination and macular lesions modeling in PHP In difficult cases or in more advanced lesions FA, OCT and ICG were performed.

A pilot trial for comparison of photodynamic therapy and transpupillary thermotherapy for the management of classic subfoveal choroidal neovascularization secondary to age-related macular degeneration.

AIM: The aim of the study was to compare the visual outcomes of photodynamic therapy (PDT) with verteporfin and transpupillary thermotherapy (TTT) for classic subfoveal choroidal neovascularization (CNVM) secondary to age-related macular degeneration (ARMD). SETTINGS AND DESIGN: Patients with subfoveal classic CNVM caused by ARMD attending vitreo-retinal services at a tertiary care setup were included in this nonrandomized, open label, prospective, clinical, comparative pilot trial. MATERIALS AND METHODS: Standardized refraction, visual acuity testing, evaluation of fundus and serial color photography and fundus fluorescein angiography were carried out to evaluate the effects of treatment in 32 eyes each undergoing either PDT or TTT. Follow-up was carried out at four weeks, 12 weeks and six months. Retreatment if indicated was carried out three months post treatment. RESULTS: Stabilization or improvement occurred in 69% of patients undergoing PDT and 50% patients undergoing TTT at six months of follow-up. Among patients with a pretreatment visual acuity greater than or equal to 20/63, only one out of six patients who underwent PDT had a drop of visual acuity > 2 lines as compared to four patients (100%) who underwent TTT. (P =0.0476, two-tailed Fisher's exact test). CONCLUSION: For short-term preservation of vision in patients of classic CNVM due to ARMD, PDT seems to be better than TTT if the pre-laser best corrected visual acuity is > 20/63 but both are equally effective if pre-laser best corrected visual acuity is < 20/63.

Transpupillary thermotherapy for the treatment of choroidal neovascularization secondary to angioid streaks.

BACKGROUND: To investigate the effect of transpupillary thermotherapy (TTT) on choroidal neovascularization (CNV) secondary to angioid streaks. METHODS: Six eyes of 5 patients with an average age of 61 years were diagnosed to have subfoveal CNV secondary to angioid streaks. Four of the CNVs were predominantly classic and 2 were occult with no classic. Visual acuity (VA) measurement, ophthalmoscopic and fluorescein angiographic examination, and optic coherence tomography (OCT) were carried out before TTT treatment and at each follow-up visit. Activity scores (AS) based on clinical, angiographic, and OCT findings were also recorded. RESULTS: The mean follow-up was 12 months. The VA initially ranged from counting fingers to 20/100 and remained stable in all patients. The mean greatest lesion diameter increased significantly from 2221 microm to 3109 microm at last follow-up (p=0.046). The mean AS decreased significantly from 6.5 to 4.8 at the 3rd month (p=0.039), but tended to increase thereafter. Retreatment with TTT was applied to 5 eyes after a mean of 7.8 months but did not decrease CNV activity as effectively as the first treatments. A fibrotic scar developed in 1 eye after the first treatment. INTERPRETATION: TTT may decrease the activity of CNVs secondary to angioid streaks in the short term, but retreatment may be necessary with unfavorable results. TTT appears to stabilize VA but not lesion size in this group of patients, which may be the natural history rather than a treatment effect.

Intravitreal bevacizumab for exudative age-related macular degeneration after multiple treatments.

BACKGROUND: Photodynamic therapy with verteporfin (PDT) significantly reduces the risk of vision loss in patients with exudative age-related macular degeneration (AMD). Indocyanine green-mediated photothrombosis (IMP) and trans-pupillary thermotherapy (TTT) may also be beneficial for selective cases of exudative AMD. However, a substantial subset of patients responds poorly to these treatments. Intravitreal bevacizumab (IVB) has been recently used in the treatment of exudative AMD, showing both visual and anatomic improvement in the majority of cases. METHODS: This interventional retrospective case series reports the effects of IVB in 17 eyes with subfoveal neovascular AMD that had undergone repeated PDT (combined or not with triamcinolone acetonide) or PDT followed by either IMP or TTT with poor results. The main outcome measures were visual acuity and tomographic signs of intra/subretinal fluid, as well as central retinal thickness. RESULTS: Most patients received a single IVB injection. The mean follow-up was 4.47 months. The mean logMAR visual acuity changed from 1.17 +/- 0.40 to 1.06 +/- 0.44 (P = 0.17). The mean central retinal thickness decreased from 404.05 +/- 245.26 to 280.23 +/- 143.14 microm (P = 0.032). At the end of the study, lack of tomographic signs of intra/ subretinal fluid was noted in four (23.5%) eyes. No ocular or systemic side effects were identified. CONCLUSIONS: Short-term results with IVB for the treatment of exudative AMD have been promising. However, the chronic retinal and pigment epithelium changes frequently present in eyes that underwent multiple previous treatments may limit complete visual recovery. To our knowledge, this is the first report on the use of IVB for this particular group of AMD patients.