Visual Acuity Outcomes after Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report Number 19.

PURPOSE: To analyze best-corrected visual acuity (BCVA) outcomes after anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD). DESIGN: Prospective cohort study of participants enrolled in a clinical trial of oral supplements and receiving anti-VEGF therapy in routine clinical practice. PARTICIPANTS: Age-Related Eye Disease Study 2 (AREDS2) participants (50-85 years of age) whose eyes met AREDS2 inclusion criteria at baseline (no late AMD, BCVA ≥20/100, no previous anti-VEGF injections) but received at least 1 anti-VEGF injection for incident neovascular AMD during follow-up. METHODS: Participants underwent refracted BCVA testing, ophthalmoscopic examination, and stereoscopic color fundus photography at baseline and annual study visits over 5 years. Self-reports of anti-VEGF injections (numbers, dates, and names of drug) were collected at baseline and annual study visits and during telephone calls every 6 months. MAIN OUTCOME MEASURES: Primary outcome measures were mean refracted BCVA and proportions of eyes with BCVA of 20/40 or better and 20/200 or worse. An exploratory outcome measure was the mean number of self-reported anti-VEGF injections. RESULTS: One thousand one hundred five eyes of 986 AREDS2 participants met the inclusion criteria; of these, 977 participants (99.1%) underwent at least 1 posttreatment visit. At the first and subsequent annual examinations after the first injection, mean refracted BCVAs were 68.0 letters (Snellen equivalent, 20/40), 66.1 letters, 64.7 letters, 63.2 letters, and 61.5 letters (Snellen equivalent, 20/60). Proportions of eyes with BCVA of 20/40 or better were 59.3%, 55.1%, 53.5%, 50.6%, and 49.7%, and those with BCVA of 20/200 or worse were 5.5%, 8.6%, 9.4%, 12.4%, and 14.4%. Mean annual numbers of self-reported anti-VEGF injections per eye were 2.9, 3.9, 3.3, 3.1, and 3.0. CONCLUSIONS: Refracted BCVA data were obtained in a clinical trial environment but were related to anti-VEGF treatment administered in normal clinical practice. Visual outcomes declined slowly with increased follow-up time: mean BCVA decreased by approximately 1.5 to 2 letters per year. At 5 years, half of eyes achieved BCVA of 20/40 or better, but approximately one sixth showed BCVA of 20/200 or worse. These data may be useful in assessing the long-term effects of anti-VEGF therapy.

Cytochrome P450 Oxidase 2C Inhibition Adds to ω-3 Long-Chain Polyunsaturated Fatty Acids Protection Against Retinal and Choroidal Neovascularization.

OBJECTIVE: Pathological ocular neovascularization is a major cause of blindness. Increased dietary intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFA) reduces retinal neovascularization and choroidal neovascularization (CNV), but ω-3 LCPUFA metabolites of a major metabolizing pathway, cytochrome P450 oxidase (CYP) 2C, promote ocular pathological angiogenesis. We hypothesized that inhibition of CYP2C activity will add to the protective effects of ω-3 LCPUFA on neovascular eye diseases. APPROACH AND RESULTS: The mouse models of oxygen-induced retinopathy and laser-induced CNV were used to investigate pathological angiogenesis in the retina and choroid, respectively. The plasma levels of ω-3 LCPUFA metabolites of CYP2C were determined by mass spectroscopy. Aortic ring and choroidal explant sprouting assays were used to investigate the effects of CYP2C inhibition and ω-3 LCPUFA-derived CYP2C metabolic products on angiogenesis ex vivo. We found that inhibition of CYP2C activity by montelukast added to the protective effects of ω-3 LCPUFA on retinal neovascularization and CNV by 30% and 20%, respectively. In CYP2C8-overexpressing mice fed a ω-3 LCPUFA diet, montelukast suppressed retinal neovascularization and CNV by 36% and 39% and reduced the plasma levels of CYP2C8 products. Soluble epoxide hydrolase inhibition, which blocks breakdown and inactivation of CYP2C ω-3 LCPUFA-derived active metabolites, increased oxygen-induced retinopathy and CNV in vivo. Exposure to selected ω-3 LCPUFA metabolites of CYP2C significantly reversed the suppression of both angiogenesis ex vivo and endothelial cell functions in vitro by the CYP2C inhibitor montelukast. CONCLUSIONS: Inhibition of CYP2C activity adds to the protective effects of ω-3 LCPUFA on pathological retinal neovascularization and CNV.

Anti-angiogenic effect of ALS-L1023, an extract of Melissa officinalis L., on experimental choroidal neovascularization in mice.

BACKGROUND: The effect of ALS-L1023, an extract of Melissa officinalis L. (Labiatae; lemon balm) leaves, on experimental choroidal neovascularization (CNV) in mice was evaluated. METHODS: C57BL/6 mice were given either vehicle or ALS-L1023 daily via oral gavage for 3 weeks (days 0-21). CNV was induced by rupturing Bruch's membrane using laser photocoagulation (day 7). Two weeks after laser injury (day 21), the CNV lesions were evaluated by an examination of choroidal flat mounts using fluorescein-labelled dextran, immunofluorescence staining with isolectin B4 and fluorescence angiography. The effects of ALS-L1023 on endothelial cell tube formation and the expression of phosphorylated extracellular signal-regulated kinase 1/2 were evaluated using human umbilical vein endothelial cells. RESULTS: The extent of CNV was reduced by ALS-L1023. Mice treated with 100 and 200 mg/kg/day of the material exhibited 44.3 and 68.1% reductions in the extent of CNV lesions, respectively, compared to the vehicle group (P < 0.001). The size of the isolectin B4-labelled area was also significantly decreased in the ALS-L1023-treated groups (P < 0.001). On fluorescein angiography, ALS-L1023-treated mice exhibited significantly less leakage of fluorescent material than did vehicle-treated mice. ALS-L1023 decreased vascular endothelial growth factor-induced human umbilical vein endothelial cell tube formation in a dose-dependent manner. The expression of phosphorylated extracellular signal-regulated kinase 1/2 was suppressed by ALS-L1023. CONCLUSIONS: The laser-induced CNV in mice can be inhibited by ALS-L1023. Therefore, it may have therapeutic potential for the treatment of diseases involving CNV.

Anti-VEGF treatment for myopic choroid neovascularization: from molecular characterization to update on clinical application.

Choroidal neovascularization (CNV) secondary to pathologic myopia has a very high incidence in global, especially in Asian, populations. It is a common cause of irreversible central vision loss, and severely affects the quality of life in the patients with pathologic myopia. The traditional therapeutic modalities for CNV secondary to pathologic myopia include thermal laser photocoagulation, surgical management, transpupillary thermotherapy, and photodynamic therapy with verteporfin. However, the long-term outcomes of these modalities are disappointing. Recently, intravitreal administration of anti-VEGF biological agents, including bevacizumab, ranibizumab, pegaptanib, aflibercept, and conbercept, has demonstrated promising outcomes for this ocular disease. The anti-VEGF regimens are more effective on improving visual acuity, reducing central fundus thickness and central retina thickness than the traditional modalities. These anti-VEGF agents thus hold the potential to become the first-line medicine for treatment of CNV secondary to pathologic myopia. This review follows the trend of "from bench to bedside", initially discussing the pathogenesis of myopic CNV, delineating the molecular structures and mechanisms of action of the currently available anti-VEGF drugs, and then systematically comparing the up to date clinical applications as well as the efficacy and safety of the anti-VEGF drugs to the CNV secondary to pathologic myopia.

The other CNVM: a review of myopic choroidal neovascularization treatment in the age of anti-vascular endothelial growth factor agents.

Choroidal neovascular membranes (CNVM) associated with pathological myopia (PM) can result in significant vision loss and legal blindness. These membranes usually occur subfoveally and are a major complication of PM, developing in approximately 5-10% of such eyes. PM is the second most common cause of choroidal neovascularization after age-related macular degeneration (AMD), and accounts for nearly 60% of CNVM cases in patients younger than age 50. Vascular endothelial growth factor-A has been implicated as the major angiogenic stimulus responsible for choroidal neovascularization secondary to AMD and several major studies have proved the benefits of anti-VEGF treatment for AMD-related CNVM. Benefits have also been observed in a number of prospective and retrospective studies evaluating PM CNVM. Despite the small differences in molecular properties of ranibizumab and bevacizumab, both drugs showed similar therapeutic effects for CNVM associated with PM. Many studies also highlighted that patient age, previous photodynamic therapy treatment, axial length, and visual acuity prior to treatment may affect treatment prognosis. Although there is a paucity of large randomized controlled trials, this systematic review highlights the large numbers of individual trials that demonstrate a significant improvement in VA. The inferior long-term results of alternative therapies, combined with an excellent safety profile from anti-VEGF treatment, make anti-VEGF the current recommended first-line therapy.

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.

Potential protective effect of angiopoietin-1 on the leakage of rat choroidal neovascularization.

OBJECTIVES: To observe the potential protective effect of angiopoietin-1 (Ang-1) on rat choroidal neovascularization (CNV) leakage. METHODS: The study was conducted at the Eye Institute of Shandong University of Traditional Chinese Medicine, Jinan, China from June 2012 to June 2013. Thirty CNV model rats were induced by laser. In vivo, fluorescein fundus angiography and pathological techniques were applied to detect the effect of vascular endothelial growth factor (VEGF) and Ang-1 intravitreous injection. In vitro, 3-(4, 5-dimethylthiazole-2-yl)-2, 5-biphenyl tetrazolium bromide (MTT) assay was applied to detect the proliferation of cultured bovine retinal endothelial cells (BRECs) after treatment with VEGF and Ang-1. Transmission electron microscopy (TEM) was used to detect the morphological changes under VEGF and Ang-1. RESULTS: In the CNV rat model, less late leakage was found in the Ang-1 group than the vehicle control or the VEGF group. The MTT assay showed Ang-1 administration inhibited the proliferation of BRECs. The VEGF promoted proliferation at low concentrations and inhibited the proliferation when its concentration reached 50 ng/ml. The administration of VEGF+Ang-1 rescued the inhibition effect of Ang-1 alone. The TEM results showed that there were less intercellular junctions in the VEGF group compared with the vehicle control. In the VEGF + Ang-1 group, the intercellular junctions were nearly normal. CONCLUSION: The Ang-1 can induce intercellular junction formation and decrease the CNV leakage.

A prospective study on different methods for the treatment of choroidal neovascularization. The efficacy of verteporfin photodynamic therapy, intravitreal bevacizumab and transpupillary thermotherapy in patients with neovascular age-related macular degeneration.

BACKGROUND: The aim of this study was to compare the efficacy of verteporfin photodynamic therapy (PDT), intravitreal injections of bevacizumab (IVB) and transpupillary thermotherapy (TTT) in patients with neovascular age-related macular degeneration (AMD). MATERIAL/METHODS: The study design was a prospective, interventional, comparative case series. Between December 2006 and March 2009, 426 eyes of 426 consecutive patients presenting with neovascular AMD were included into the study. Patients presented with subfoveal CNV predominantly classic, minimally classic, and occult with no classic component; lesion size less than 5000 µm in the greatest linear dimension, and the area of hemorrhages ≤1/3 were randomized to receive either PDT (group I) or IVB (group II) in a 1:1 ratio. Other patients with CNV were included into the group III and received TTT. RESULTS: One hundred eyes were treated with PDT. Mean baseline logMAR BCVA was 0.62 and final visual acuity decreased to 0.74 (p<0.05, Wilcoxon test); 104 eyes were treated with IVB. Mean baseline BCVA was 0.82 and final visual acuity increased to 0.79 (p>0.05, Wilcoxon test); 222 patients were treated with TTT. Mean baseline BCVA was 1.10 and final visual acuity decreased to 1.15 (p>0.05, Wilcoxon test). Among all eyes the average number of treatment sessions was 2.34 (SD 1.17). CONCLUSIONS: Our study shows that IVB injections had the best efficacy in the improvement of final BCVA. However, both IVB and TTT demonstrated good stabilization of vision. Although after PDT final BCVA was significantly worse from baseline, it may also be beneficial for some patients with neovascular age-related macular degeneration.

RPE cell senescence: a key contributor to age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness in industrialized countries. Although much progress has been made recently in the management of later stages of the disease, no agents have yet been developed for the early stages or for prophylactic use. Furthermore, even the treatments for the later stages have limited effectiveness. The process of developing improved treatments for AMD is complicated by the existence of several theories concerning the cause of the disorder, each suggesting a different strategy for finding effective therapeutics. One of the potential contributors to AMD pathology is retinal pigment epithelial (RPE) cell senescence. The present paper hypothesizes that RPE senescence plays a central role in the etiology of AMD. This hypothesis is supported by the ability of RPE cell senescence to account for the signs, risk factors, and successful treatment modalities of the disorder. This hypothesis also points to several new prophylactic and treatment strategies for AMD.

Vision-related function after low-dose transpupillary thermotherapy versus photodynamic therapy for neovascular age-related macular degeneration.

PURPOSE: To compare the effects of low-dose transpupillary thermotherapy (TTT) and verteporfin photodynamic therapy (PDT) on patient-reported visual function using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) in patients with occult neovascular age-related macular degeneration (AMD). METHODS: Patients were randomized to receive either low-dose TTT (and sham PDT) (n = 52) or PDT (and sham TTT) (n = 46). Patients were followed for 12 months with retreatment according to clinical assessment. The clinical outcome of this study has been recently reported. The NEI VFQ-25 questionnaire was administered at baseline and at 12 months. RESULTS: Forty-two patients (80.1%) in the TTT group and 37 patients (80.0%) in the PDT group completed the questionnaire at the 12-month follow-up. The mean change in the NEI VFQ-25 composite score was +1.2 for the TTT group (p > 0.05) and +0.7 for PDT group (p > 0.05). None of the subscale categories showed significant changes between treatment groups at 12 months. Subgroup analysis showed that NEI VFQ-25 scores were lower in patients treated in their better-seeing eye. CONCLUSION: In this randomized study on patients with occult neovascular AMD, low-dose TTT and PDT appeared to be equally potent at stabilizing patient-reported visual function. However, the study was underpowered for this conclusion to be made firmly. Also, given the impressive results obtained with ranibizumab for all types of neovascular AMD, neither PDT nor low-dose TTT should be considered as first-line treatments.

Association of systemic steroids and mycophenolate mofetil as rescue therapy for uveitic choroidal neovascularization unresponsive to the traditional immunosuppressants: interventional case series.

To study the efficacy of systemic steroids (SS) associated with mycophenolate mofetil (MMF) for the control of juxta/sub-foveal uveitic choroidal neovascularization (CNV) unresponsive to the traditional immunosuppressive agents. Patients with juxta/sub-foveal uveitic CNV unresponsive to the traditional immunosuppressive drugs were treated with SS and MMF. The study was designed as a prospective, consecutive, open-label, interventional case series. Visual gain and loss were defined as improving or worsening of two or more lines of best-corrected visual acuity (BCVA), respectively. CNV size outcome was dichotomized as "increased" or "stable/reduced", if increased >200 µm(2), or reduced ≥ 200 µm(2) or not modified by 200 µm(2), respectively. Nine cases (12 eyes) have been considered; ages ranged from 27 to 56 years. The mean follow-up time was 18.2 ± 2.9 months (min: 14 months, max: 23 months). At base-line, the mean BCVA was 0.3 ± 0.17, improving up to 0.57 ± 0.25 and to 0.63 ± 0.22 (P < 0.001, paired t-test) at the 6 and 12-month follow-ups, respectively. At the last follow-up, all the patients had stable/improved BCVA (P < 0.0001, Fisher's exact test) and stable/reduced lesion size (P < 0.0001, Fisher's exact test). None of the patients complained of any severe adverse event during the treatment. The combination of SS and MMF seems to be a promising strategy in order to control uveitic CNVs unresponsive to the traditional immunosuppressive agents. Further studies are needed to validate the data of this case series.

Effects of oral administration of Stephania tetrandra S. Moore on neovascularization of retinal and choroidal capillaries of diabetes in rats.

In rats, an injection of streptozotocin (STZ) elevated blood levels of glucose 4 weeks later (STZ-induced diabetes) and an over-production of microvessels of retinal and choroidal capillaries of eyes developed. A previous study has shown that administration of Stephania tetrandra S. Moore (STSM) in culture prevented the over-production of microvessels of those capillaries of STZ-induced diabetes in vitro. Therefore, the study investigated whether or not orally administered STSM could inhibit over-production of microvessels of those capillaries of STZ injected rats in vivo. When STSM was given at the same time as the STZ injection and continued daily for 7 weeks, STSM prevented the elevation of blood glucose level and over-production of microvessels of those capillaries. When STSM was given after elevation of blood glucose level of glucose (4 weeks after STZ injection) and continued daily for 4 weeks, STSM lowered the elevated blood glucose level but had no effect on the over-production of microvessels of those capillaries. It was inferred that deposition of N(epsilon)(carboxymethyl) lysine in retinal and choroidal tissues, which is induced by STZ-induced diabetes may deteriorate the blood-retinal barrier and the blood-choroidal barrier. One might, therefore, speculate that advanced STZ-induced diabetes may deteriorate the blood-retinal barrier and blood-choroidal barrier. Therefore, STSM may not reach the retinal and choroidal tissues in the posterior ocular region in vivo.

Transpupillary thermotherapy in chinese patients with choroidal neovascularization secondary to age-related macular degeneration: emphasis on the influence of power setting.

PURPOSE: To perform a safety and efficacy study of transpupillary thermotherapy (TTT) in Chinese patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD). METHODS: In a prospective study, patients with subfoveal or juxtafoveal CNV secondary to ARMD underwent TTT with fixed treatment and follow-up protocols. From August 2002 to December 2004, 26 patients (27 eyes) completed > or =6 months of follow-up and were included in this report. RESULTS: Fourteen eyes (52%) had improved or stable visual acuity (loss of <3 lines) and 13 eyes (48%) had vision loss of > or =3 lines. The serial mean visual acuity initially decreased during follow-up, then stabilized by 6 months. In the subgroup of occult or minimally classic CNV (20 eyes), 13 eyes (65%) had improved or stable vision. The major complication of TTT included laser-related retinal pigment epithelium (RPE) atrophy in 10 eyes (37%). Six eyes had mild RPE atrophy, 4 eyes had severe RPE-choroid atrophy (macular burn). Analysis of possible risk factors for macular burn showed that 3 eyes had to have the power amplified due to nuclear sclerosis, and 1 pseudophakic eye had regular power. CONCLUSIONS: TTT in Chinese ARMD patients with occult or minimally classic CNV, according to our protocol, prevented severe vision loss in the majority of patients, but power amplification due to medium lens opacity induced RPE atrophy or burn in some patients.

Low-power transpupillary thermotherapy combined with intravitreal triamcinolone acetonide for subfoveal choroidal neovascularization.

PURPOSE: To examine transpupillary thermotherapy combined with intravitreal triamcinolone for treatment of subfoveal choroidal neovascularization. METHODS: The clinical interventional, noncomparative, case series study included 14 patients (14 eyes) with choroidal neovascularization (age-related macular degeneration, n = 11; high myopia, n = 2; unknown reason, n = 1), who underwent transpupillary thermotherapy (75-150 mW, 60 s, 500-3,000 microm), followed by an intravitreal triamcinolone injection (10 mg). Follow-up was at least 6 months. RESULTS: Visual acuity increased by 3 lines in 3 (21%) eyes at 3 months, and in 3 (21%) eyes at 6 months of follow-up. None of the patients experienced a visual acuity loss of 3 or more lines. At the 6-month follow-up, mean visual acuity was improved by 1.36 +/- 1.16 lines. Retreatment by transpupillary thermotherapy was performed for 3 (21%) eyes at 3 months, and for 1 (7%) eye at 6 months of follow-up. CONCLUSIONS: Transpupillary thermotherapy combined with intravitreal triamcinolone may be a therapeutic option for choroidal neovascularization particularly if other treatment modalities are not available.

Transpupillary thermotherapy for the treatment of choroidal neovascularization in age-related macular degeneration in Taiwan.

PURPOSE: To evaluate the therapeutic outcome and the recurrence of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) after transpupillary thermotherapy (TTT) in light-brown retinas. METHODS: A retrospective, non-randomized study of 58 eyes in 55 patients with subfoveal CNV treated with TTT was conducted. Power settings were set about half the value for Caucasian eyes. The outcome was assessed with best-corrected visual acuity, fluorescein angiography, indocyanine green angiography, and fundoscopic examination. RESULTS: Forty-four membranes were occult, six classic, and eight mixed. Mean follow-up was 16.6+/-10.7 months (range: 6-48 months). Membranes closed in 46 eyes. Iatrogenic complications included three subretinal haemorrhage, two retinal pigment epithelium tears, and two macular area cystic changes. In eyes with occult CNV, visual acuity improved in six (13.6%), 14 (31.8%) remained unchanged, and 24 (54.6%) deteriorated. For various CNV, average logMAR changes from baseline at last follow-up were 0.30 in occult, -0.08 in classic, and 0.59 in mixed (P<0.01). Thirty eyes experienced recurrence within 9.2+/-6.2 months (range: 2-22 months). Cumulative recurrence rate was 45% at 12 months and 71% at 22 months, with no significant difference between occult and non-occult type CNV. CONCLUSIONS: Transpupillary thermotherapy does not cure CNV secondary to AMD. High recurrence was found independent of CNV type. Most improved vision was found mostly in classic CNV. Complications associated with high energy level should be considered in light-brown retinas.

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.

Photodynamic therapy of subfoveal choroidal neovascularization secondary to reticular pattern dystrophy: three-year results of an uncontrolled, prospective case series.

PURPOSE: To investigate the effects of photodynamic therapy (PDT) on subfoveal choroidal neovascularization (CNV) secondary to reticular pattern dystrophy (RPD) of the retinal pigment epithelium. DESIGN: Open-label, prospective, interventional case series. METHODS: Thirteen eyes diagnosed with subfoveal CNV associated with RPD were considered. Complete ophthalmic examinations were performed at baseline and thereafter at three-month intervals for three years. Primary outcome measure was the number of eyes with <15 letters loss (approximately <3 lines) at 12, 24, and 36 months, compared with baseline. Secondary outcome measures included CNV progression and number of PDT sessions. RESULTS: Seven eyes showed a decrease in best-corrected visual acuity of at least three lines at three-year examination. Each eye received a median number of treatments of two, zero, and zero in years one, two, and three, respectively. CONCLUSIONS: PDT does not appear to guarantee long-term vision stabilization in RPD-related subfoveal CNV, and alternative therapies should be investigated.

Retinal function following transpupillary thermotherapy for occult choroidal neovascularization in age-related macular degeneration: a short-term study by focal electroretinography.

PURPOSE: To assess short-term changes in macular function after transpupillary thermotherapy (TTT) in patients with occult subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD), using focal electroretinography (FERG). METHODS: Twenty-five patients with occult subfoveal CNV due to AMD were treated with TTT delivered using an infrared (810 nm) diode laser (spot size 3.0 mm, laser power 400-600 mW, duration 60 seconds). All patients were clinically evaluated before, 1 and 6 weeks after treatment. Snellen visual acuity (VA) was measured at each visit. Fluorescein angiography (FA) was performed at baseline and 6 weeks after TTT. Focal ERGs were recorded in all patients immediately before and 1 week after TTT in response to an 18-degree diameter, 41 Hz flickering spot (630 nm) centred on the fovea, presented on a steady background in Maxwellian view. A subgroup of 12 patients was also re-tested by FERG at 6-weeks post-TTT. RESULTS: No significant changes in mean FERG amplitude and phase were observed across the different recording sessions before and after TTT. One week after TTT, four patients had significant (> 2 SD from baseline variability) increases in FERG amplitude and/or phase advances, one had a decrease in amplitude and four had phase delays, compared to baseline. The remaining 15 patients had stable FERGs. Six weeks after TTT, four patients had significant increases in FERG amplitude and/or phase advances, four had decreases in amplitude and/or phase delays, and four had stable FERGs, compared to baseline. Improvement in FERG parameters after TTT was always associated with an improvement in VA and a decrease in exudation. Patients with post-TTT FERG deterioration had stable or deteriorated clinical pictures. At either 1 or 6 weeks post-TTT, the FERG amplitude increase was inversely correlated (p < 0.05) with the baseline FERG amplitude and VA. CONCLUSIONS: Three major conclusions can be drawn: in a short-term follow-up, TTT was not found to be associated with significant changes in macular function; FERG improvement was associated with VA improvement, and the increase in FERG amplitude was greatest in patients with the worst baseline acuity.

Long term results after transpupillary thermotherapy in eyes with occult choroidal neovascularisation associated with age related macular degeneration: a prospective trial.

AIM: To evaluate long term results after transpupillary thermotherapy (TTT) in eyes with exudative age related macular degeneration. METHODS: In a prospective clinical study eyes with occult or predominantly occult choroidal neovascularisation and no pretreatment were scheduled to have a TTT with a power of 630 mW. Visual acuity for far and near distances as well as contrast sensitivity were evaluated 6, 12, and 24 months postoperatively and statistically analysed. RESULTS: 47 eyes fulfilled the inclusion criteria. Overall, 70% of the patients showed an improved (14%) or had unchanged (56%) ETDRS vision after 24 months. Reading vision was stabilised (51%) or better (5%) in 56% of the eyes at this time. However, the increasing number of eyes with severe deterioration resulted in a significant decrease of both parameters over time (p = 0.0002 and p = 0.0003, respectively). Contrast sensitivity could be maintained (70%) or improved (9%) in 79%. Statistical analyses indicated a trend but no significant decrease over time (p = 0.056). CONCLUSION: Although in the majority of patients far and near distance acuity could be stabilised on average a significant decrease over time after TTT was observed. Statistical comparison of months 12 and 24 showed no further deterioration.

Low power vs standard power transpupillary thermotherapy in patients with age-related macular degeneration and subfoveal choroidal neovascularization ineligible for photodynamic therapy.

AIM: To assess the effect of standard power vs low power transpupillary thermotherapy (TTT) in patients with active subfoveal choroidal neovascularization secondary to age-related macular degeneration ineligible for photodynamic therapy (PDT) by original treatment of age-related macular degeneration with photodynamic therapy (TAP) study group recommendations. METHODS: Retrospective review of 79 patients with active predominantly occult subfoveal choroidal neovascularization or predominantly classic subfoveal choroidal neovascularization but Snellen visual acuity <20/200. All patients were treated with TTT administered via a Mainster wide field fundus contact lens with a retinal power/diameter coefficient of 248 mW/mm in the standard power (n=27) and 181 mW/mm in the low power group (n=52). The primary outcome was stabilization (<1 Snellen line change) or improvement (two or more Snellen lines) in visual acuity. Clinical and fluorescein angiographic resolution of overlying exudation was documented. RESULTS: At 24 month follow-up, 17 patients (63%) in the standard power and 36 patients (69%) in the low power group achieved stable or improved vision. Improved vision (mean three lines) was observed in 22% of the standard power and 23% of the low power group. Overlying exudation was reduced clinically with minimal or no leakage on fluorescein angiogram in 85% of standard power and 90% of low power group. Subgroup analysis in the low power group demonstrated a visual benefit in patients with subfoveal lesions, which had any classic component. CONCLUSIONS: Low power TTT is as effective as standard power in stabilizing or improving vision and reducing overlying exudation in patients with active subfoveal choroidal neovascularization ineligible for PDT.