RETROSPECTIVE REVIEW OF LUCENTIS "TREAT AND EXTEND" PATTERNS AND OUTCOMES IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To assess patterns and outcomes of a "Treat and Extend" dosing regimen of ranibizumab in patients with age-related macular degeneration. METHODS: Three hundred and thirty two treatment-naive age-related macular degeneration patients starting therapy with ranibizumab between January 1, 2011, and June 30, 2012, at the Ivey Eye Institute were reviewed, and 79 met inclusion criteria. Patients on Treat and Extend dosing regimen underwent an induction phase with monthly injections and then moved onto an extension phase. Change in visual acuity and central retinal thickness during the induction and extension phases were recorded. RESULTS: During the induction phase, patients had a significant gain in vision and decrease in central retinal thickness (+8.4 letters, P < 0.001 and -81.3 µm, P < 0.001). During the extension phase, patients did not have significant change in vision (-0.5 letters, P = 0.81) and did not have significant change in central retinal thickness (-11.5 µm, P = 0.17). The average extension interval between treatments was 47.7 days, with patients receiving an average of 8.6 injections per year. Cost analysis showed it cost US $16,659 to treat 1 patient in the first year on Treat and Extend dosing regimen compared with US $20,614 on monthly dosing. CONCLUSION: Treat and Extend dosing regimen allows similar visual outcomes to monthly dosing, while reducing the total number of injections, visits, and overall cost.

LONG-TERM OUTCOMES FOR OPTIC DISK PIT MACULOPATHY AFTER VITRECTOMY.

PURPOSE: To evaluate the efficacy of pars plana vitrectomy for congenital optic disk pit maculopathy with various adjuvant techniques, including gas tamponade, internal limiting membrane peel, and temporal optic disk endolaser in a multicenter study with long-term follow-up. METHODS: A retrospective chart review was performed to identify eyes that underwent surgical repair for congenital optic disk pits and serous macular detachment with or without macular retinoschisis from four retinal centers across Canada from 2003 to 2013. Data collected included surgeries performed, preoperative and postoperative vision, central retinal thickness, and presence or absence of subretinal fluid. Optical coherence tomography was used to define anatomical success (i.e., foveal reattachment). RESULTS: Thirty-two eyes of 32 patients with optic disk pits and serous macular detachments were identified that had undergone surgical repair. All eyes underwent pars plana vitrectomy and induction of posterior vitreous detachment if one was not present. Additional procedures performed on occasion included internal limiting membrane peel (n = 8), temporal optic disk pits endolaser (n = 7), and gas tamponade (air, C3F8 or SF6; n = 31). After vitrectomy surgery, foveal attachment was achieved in 26 of 32 eyes (81.3%). The average number of surgeries required was 1.4 ± 0.6, with a maximum of 3 vitrectomies (n = 2). Mean change in best-corrected visual acuity was -0.47 ± 0.54 logMAR units, which corresponds to approximately 5 lines of visual improvement (P < 0.001). Median time to reattachment was 416 days. Preoperative vision, preoperative symptom days, and age were not associated with postoperative reattachment. Similarly, internal limiting membrane peel and temporal endolaser were not associated with postoperative reattachment, nor was there a difference between air and SF6 and C3F8 gas tamponade. Elevated preoperative central retinal thickness was associated with a lower chance of postoperative reattachment (P = 0.007) and was also the best prognostic indicator of success (P = 0.039). CONCLUSION: Vitrectomy for macular detachment due to optic disk pit has good long-term success and results in an improvement in visual acuity. However, adjuvant techniques such as internal limiting membrane peel and temporal endolaser may not improve outcomes, nor does there seem to be a difference between short- and long-acting gases. Patients should be made aware that it can take more than a year and multiple surgeries to achieve foveal reattachment and that increased baseline central retinal thickness is a poor prognostic sign.

Patterns of anti-vascular endothelial growth factor discontinuation in neovascular age-related macular degeneration.

OBJECTIVE: To report on anti-vascular endothelial growth factor (anti-VEGF) discontinuation in neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naive nAMD patients initiating anti-VEGF injections between 2015 and 2021. METHODS: Demographics, treatment start and end dates, number of injections, treatment length, reason for discontinuation, and baseline and final data (i.e., age, best-corrected visual acuity, and central subfield thickness) were recorded. Statistical analyses using STATA 17.0 assessed differences between baseline and final values and between treatment-discontinuation subgroups. RESULTS: A total of 619 eyes of 502 treatment-naive patients (9015 injections) were included (age, 81.6 ± 8.4 years; 64.0% female). Discontinuation rate was 58.3% (361 of 619), with 310 patients discontinuing because of the lack of visual benefit (n = 152), severe comorbidity or death (n = 82), transferred (n = 33), stable off active treatment (n = 19), lack of benefit plus stable off treatment (n = 14), patient decision (n = 6), and ocular comorbidity (n = 4). Among the 309 remaining patients, 51 (16.5%) were lost to follow-up. Discontinuation occurred within the first year in 49.3% (n = 178). Visual acuity was at least maintained in all groups and improved in the following groups: severe comorbidity or death (p < 0.0001), lost to follow-up (p = 0.0003), transferred (p = 0.0004), and stable off treatment (p = 0.0053). The lack of visual benefit group had no improvement in vision regardless of treatment length. Compared with other subgroups, those stable off treatment group was younger (p = 0.0055), had better baseline vision (p = 0.0018), received more injections (p = 0.0437) over a longer time (p = 0.0034), and achieved better final vision (p < 0.0001). CONCLUSION: While there was a high discontinuation rate over 7.5 years, most were attributable to disease or treatment factors and nonmodifiable patient factors. Discontinuation frequently occurred within the first year.

WAS IT LEUCONOSTOC SPECIES? A CASE OF DELAYED-ONSET ENDOPHTHALMITIS PRESENTING 14 YEARS AFTER CATARACT SURGERY.

PURPOSE: To report a case of delayed-onset endophthalmitis presenting 14 years after an uncomplicated cataract surgery. METHODS: Case report. RESULTS: An 89-year-old pseudophakic man complained of redness and reduced visual acuity in his right eye. He had no history of trauma or systemic infection, and his only surgery on the right eye was an uncomplicated cataract surgery 14 years before. On physical examination, he was found to have keratic precipitates and a white posterior capsular plaque in the right eye. He was treated with a right pars plana vitrectomy and intraocular lens removal. Microbiological classification of the samples revealed the presence of a Leuconostoc species within the vitreous humor and coagulase-negative staphylococci on the lens. Two months after placement of the intraocular lens, he achieved a best-corrected visual acuity of 20/200 in his right eye. CONCLUSION: To the best of our knowledge, this is the first reported case of delayed-onset endophthalmitis occurring more than 10 years after an uncomplicated cataract surgery. This case highlights a highly unusual presentation of delayed-onset endophthalmitis and reports a potential novel microbiological cause of plaque formation.

Treatment discontinuation patterns of anti VEGF in retinal vein occlusion.

OBJECTIVE: The purpose of this research is to report on real-world anti-vascular endothelial growth factor (anti-VEGF) treatment patterns in retinal vein occlusions (RVO). DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naive RVO patients initiating anti-VEGF injections between 2015 and 2021. METHODS: Medical records available until June 2022 were reviewed. Demographics, diagnosis, number of injections, treatment length, reason for discontinuation, and baseline and final data (e.g., date, age, best-corrected visual acuity [BCVA], and central subfield thickness) were recorded. Statistical analyses performed with STATA 17.0 assessed differences between baseline and final values, branch (BRVO) and central retinal vein occlusion (CRVO), and treatment-discontinuation subgroups. RESULTS: A total of 219 treatment-naive eyes were included (70.3 ± 13.2 years of age, 52.5% female), with 99 BRVOs and 120 CRVOs (2482 injections). The discontinuation rate was 76.7% (168 of 219), with 72.7% of patients (77 of 99) with BRVOs and 75.8% of patients (91 of 120) with CRVOs discontinuing injections. Reasons for discontinuation included stable off active therapy (98 eyes), severe comorbidity or death (17 eyes), switched to intraocular steroid (implant or injection) (12 eyes), lack of visual benefit (10 eyes), ocular comorbidity (5 eyes), patient decision (5 eyes), and patient transfer (5 eyes). Among the remaining 67 eyes, 16 (24%) were lost to follow-up. Reasons for discontinuation differed between BRVO and CRVO patients (p = 0.002). Eyes with CRVO presented with worse BCVA (p < 0.0001) and achieved worse final BCVA (p < 0.0001), but both groups experienced improvements (p < 0.0001). Younger age, better baseline BCVA, and a diagnosis of BRVO were independent predictors of better final visual acuity. CONCLUSION: Over 7.5 years, treatment was discontinued for three-quarters of RVOs. Stable disease was the most common reason for discontinuation, with nearly half (45%) of all RVOs in the cohort stable off active therapy. Better visual outcomes were achieved in BRVO than in CRVO, although both groups benefited from treatment.

Acupuncture resulting in eye penetration and proliferative vitreoretinopathy - Surgical and medical management with intraocular methotrexate.

PURPOSE: To highlight the surgical and medical management used in an extensive globe penetrating injury caused by an acupuncture needle. OBSERVATIONS: We report on a case of acupuncture treatment error resulting in needle penetration of the eye, retinal detachment, and progressive post-traumatic proliferative vitreoretinopathy (PVR). This patient required aggressive surgical management with multiple vitrectomies along with adjunctive intravitreal methotrexate to control ongoing PVR. At last follow-up, 15 months after presentation, the patient's BCVA was 20/40 and the periphery was flat with fibrosis stable. CONCLUSIONS AND IMPORTANCE: Open globe injuries are a subtype of ocular trauma which can cause irreparable vision loss. This case highlights the extensive potential complications which can occur following traumatic injury to the retina and choroid, as well as the role of both surgical and medical management of retinal detachment and PVR. In addition, this is the first report of the use of off-label adjunctive intravitreal methotrexate to control post-traumatic PVR. Further research into this treatment approach could reveal a role of adjunctive methotrexate in the management of such injuries.

Effectiveness and safety of ranibizumab 0.5 mg in treatment-naïve patients with diabetic macular edema: Results from the real-world global LUMINOUS study.

PURPOSE: To assess the one-year effectiveness and safety of ranibizumab 0.5 mg in treatment- naïve patients with diabetic macular edema (DME) enrolled in the real-world LUMINOUS study. PATIENTS AND METHODS: A 5-year, prospective, observational, open-label, global study which recruited 30,138 patients across all approved indications. Consenting patients (≥18 years) who were treatment-naïve or previously treated with ranibizumab or other ocular treatments were treated as per the local ranibizumab label. Here, we present the change in visual acuity (VA) (Early Treatment Diabetic Retinopathy Study letter score; primary treated eye) at Year 1, as well as the change in VA based on injection frequencies (≤4 and ≥5), treatment exposure, and the overall adverse events (AEs) and serious AEs (SAEs) in treatment-naïve DME patients. RESULTS: Of the 4,710 DME patients enrolled in the study, 1,063 were treatment-naïve. At baseline, mean age was 64.5 years, 54.7% were male, and 69.2% were white. At 1 year, mean VA letter score improved by +3.5 (n = 502) from a baseline of 57.7 with a mean of 4.5 injections. Presented by injection frequencies ≤4 and ≥5, VA letter score gains were 0.5 (n = 264) and 6.9 (n = 238) from baseline letter scores of 56.6 and 59.0, respectively. Over 5 years, the incidence of ocular/non-ocular AEs and SAEs was 7.2%/10.1% and 0.3%/5.8%, respectively. No endophthalmitis cases were reported. CONCLUSIONS: The LUMINOUS study included patients with DME with more diverse baseline characteristics than those in randomized clinical trials. The 1-year data showed improvement in VA with low number of injections in treatment- naïve patients with DME. Greater VA gains were observed in patients who received ≥5 injections. No new safety findings were identified. LUMINOUS confirms the effectiveness and safety of ranibizumab for the treatment of patients with DME in a real-world clinical practice.

Two-year analysis of changes in the optic nerve and retina following anti-VEGF treatments in diabetic macular edema patients.

Purpose: To evaluate long-term structural and functional changes that happen to the optic nerve and retina following ranibizumab (Lucentis) injections in diabetic macular edema (DME) patients. Methods: Patients with clinically significant DME requiring anti-VEGF injections underwent pre-injection baseline, 6, 12, and 24 month follow-up tests. The tests performed were optical coherence tomography (OCT), best-corrected visual acuity (BCVA), and visual field (VF). Wide-field fluorescein angiogram (IVFA) was performed to monitor the progression of diabetic ischemia. Results: A total of 30 patients requiring anti-VEGF injections and 21 control patients not requiring anti-VEGF injections were enrolled in the study. From baseline, the average macular thickness significantly decreased (p<0.0002) over the 24-month time period. Mean perfused ratio significantly increased (p<0.0005) at 6, 12, and 24 months. Cup volume and vertical cup-to-disk ratio significantly increased (p<0.0014) over the study period. This was verified by masked independent grading of patient optic nerve stereo-photographs by glaucoma specialists. BCVA significantly (p<0.0006) improved over the study period. VFs showed a non-significant trend of deteriorating peripheral vision at 12 and 24 months. Conclusion: Clinically, anti-VEGF therapy appears to affect the optic nerve by increasing cup volume and increasing vertical cup/disk ratio over time. The results provide a cautionary note to monitor both the retina and optic nerve status in patients undergoing frequent injections.

Safety of anti-VEGF treatments in a diabetic rat model and retinal cell culture.

PURPOSE: To analyze the safety of different concentrations of anti-VEGF on retinal cells. METHODS: Non-diabetic and streptozotocin (STZ)-induced diabetic rats received intravitreal rat anti-VEGF injections that had final vitreous concentrations of 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL. Rats were also injected with the clinical dose of ranibizumab. TUNEL assay was performed on sectioned eyes to evaluate apoptotic cells. In vitro, rat retinal cell cultures were exposed to 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL of ranibizumab for 48 and 72 hrs. Cellular metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, necrosis by lactate dehydrogenase (LDH), and apoptosis by cell death enzyme-linked immunosorbent assay (ELISA). RESULTS: Diabetic rats had a significant increase (p<0.03) in apoptotic cell death at half the clinical dose, at the clinical dose, and at double the clinical dose. In vitro, MTT showed a significant decrease (p<0.04) in cellular metabolic activity at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. LDH showed a significant increase (p<0.04) in necrosis at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. ELISA showed a significant increase (p<0.04) in apoptosis at half the clinical dose, at the clinical dose, and double the clinical dose, compared to control at 48 and 72 hrs. CONCLUSIONS: Anti-VEGF treatment may be potentially detrimental to the retina by decreasing cellular metabolic activity and increasing cytotoxicity of retinal cells. The results provide a cautionary note to monitor both the retina and optic nerve status in patients undergoing frequent injections.

Evaluation of the side effects and image quality during fluorescein angiography comparing 2 mL and 5 mL sodium fluorescein.

BACKGROUND: Although intravenous fluorescein angiography (IVFA) is a relatively safe procedure, side effects have been shown to occur. The designed purpose of this study was to demonstrate a reduction in the frequency and severity of side effects during digital IVFA using 2 mL compared with 5 mL of 10% sodium fluorescein (NaFl). The secondary hypothesis was to show that no loss of image quality occurred with a reduction in the NaFl dose utilizing digital fluorescein angiography. METHODS: A prospective study was initiated in which 1200 patients were randomized to 2 mL or 5 mL of 10% NaFl to allow for the evaluation of adverse events. Standard IVFA technique utilizing modern high-resolution digital photography was employed. Photographers evaluated the difficulty of image capture. A masked observer recorded all adverse events. Masked ophthalmologists evaluated image quality subjectively with a 4-point rating scale. Secondary to concerns regarding image quality, a masked interim analysis was carried out after 140 patients had been randomized. RESULTS: A statistically significant reduction in the quality of angiograms (p = 0.0025) and ease of photography (p = 0.0012) was associated with 2 mL of NaFl, necessitating the termination of the study. Patients randomized to the 5 mL NaFl group experienced all 3 of the minor adverse events in the study. No statistically relevant conclusions could be obtained from this limited group. INTERPRETATION: Two millilitres of NaFl for IVFA produces inferior quality digital images compared with 5 mL of NaFl. The potential reduction in adverse events associated with 2 mL of NaFl becomes unimportant in light of this significant finding regarding image quality.

Triamcinolone acetonide as adjunctive treatment to verteporfin in neovascular age-related macular degeneration: a prospective randomized trial.

PURPOSE: To examine the use of intravitreal triamcinolone acetonide (IVTA) as adjunctive therapy to photodynamic therapy (PDT) in the treatment of occult and minimally classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN: Single-center prospective randomized pilot clinical trial. PARTICIPANTS: Thirty eyes of 30 patients with occult or minimally classic CNV secondary to AMD. METHODS: Patients were randomized prospectively to receive either PDT alone or combined PDT plus IVTA treatment for CNV secondary to AMD. Standard verteporfin PDT was performed in all patients. In the PDT plus IVTA group, a 12-mg intravitreal injection of triamcinolone acetonide was given 30 minutes after PDT. Active lesions were retreated every 3 months for 1 year. MAIN OUTCOME MEASURES: Change in visual acuity and retreatment rate. RESULTS: Mean visual acuity remained stable in the PDT plus IVTA group (-1.9 Early Treatment Diabetic Retinopathy Study [ETDRS] letters; P = 0.58), but declined significantly in the PDT alone group (-13.3 ETDRS letters; P = 0.02). The treatment rate was 1.13 in the PDT plus IVTA group and 3.6 in the PDT alone group (P<0.0001). Mean contrast sensitivity increased by 3.6 letters (P = 0.09) in the PDT plus IVTA group and decreased by -1.84 letters (P = 0.07) in the PDT alone group. Cataract progression was noted in 4 of 7 phakic eyes in the PDT plus IVTA group. Six patients (40%) in the combined PDT plus IVTA group required topical glaucoma therapy for control of elevated intraocular pressure. CONCLUSIONS: This pilot study demonstrated effective stabilization of visual acuity and reduced treatment frequency at 12 months with combination PDT plus IVTA therapy versus PDT alone. Larger randomized trials are ongoing to determine the efficacy and risks of PDT with IVTA.

Development of macular hole in the early postoperative period following pneumatic retinopexy.

Pneumatic retinopexy is a minimally invasive procedure used to repair uncomplicated superior rhegmatogenous retinal detachments. Macular holes have been reported in only 6 cases as a rare sequel to this procedure. The development of macular hole in a patient in the early perioperative period following pneumatic retinopexy is described.

An otherwise healthy young man presents with bilateral CRVO as the first sign of hyperviscosity syndrome in the setting of new multiple myeloma.

PURPOSE: To report a case of bilateral central retinal vein occlusion as the presenting feature of new onset multiple myeloma in an otherwise healthy man. METHODS: A 44-year-old man presented with painless visual changes in his left eye. Ophthalmic examination revealed what appeared to be bilateral central retinal vein occlusion and hematologic assessment resulted in the diagnosis of immunoglobulin G multiple myeloma. RESULTS: Initial management was plasma exchange followed by a chemotherapy regimen of cyclophosphamide, bortezomib, and dexamethasone, and subsequent plans for bone marrow transplant. CONCLUSION: Hyperviscosity syndrome seems similar to central retinal vein occlusion and may be associated with systemic conditions such as diabetes and atherosclerosis; however, alternative etiologies should be considered in young otherwise healthy individuals. This case underscores the need for diligent and thorough investigations for less common systemic conditions associated with retinal vein occlusions by primary care ophthalmologists.

Late retinal neovascularization after central retinal vein occlusion: a case report and literature review.

PURPOSE: To present the case of a 59-year-old man with central retinal vein occlusion with limited retinal ischemia who developed retinal neovascularization over a year after initial presentation. METHODS: Retrospective case report. RESULTS: On initial presentation, the patient had counting fingers vision in the affected eye and significant macular edema. After 4 intravitreal ranibizumab injections, his vision improved to 20/30. An intravenous fluorescein angiography performed at presentation and at a 4-month follow-up revealed limited retinal ischemia and no neovascularization. Over a year after his initial presentation, the patient returned with visual symptoms and was found to have subhyaloid hemorrhage and areas of retinal neovascularization. CONCLUSION: Anterior and posterior segment neovascularization after central retinal vein occlusion has traditionally been thought to occur within a few months of the inciting event. However, the use of antivascular endothelial growth factor agents may alter the angiogenic processes within an eye after central retinal vein occlusion, potentially delaying the onset of neovascularization. This suggests the need for enhanced monitoring in this patient population.

Comparison of outcomes after switching treatment from intravitreal bevacizumab to ranibizumab in neovascular age-related macular degeneration.

OBJECTIVE: To compare visual acuity and central retinal thickness in patients initially treated with bevacizumab (Avastin) and switched to ranibizumab (Lucentis) for neovascular age-related macular degeneration (AMD). DESIGN: A retrospective chart review. PARTICIPANTS: This study included 87 eyes from 80 patients over the age of 65 with neovascular AMD. METHODS: Patients were initially treated with bevacizumab injections every 6 weeks and then switched to ranibizumab every 4 weeks when it became publicly funded by the Ontario government. Outcomes include comparison of visual acuity and central retinal thickness after bevacizumab treatment, and after switching to ranibizumab. RESULTS: Visual acuity improved significantly versus initial baseline values following a treatment course of 3 or more injections of bevacizumab (0.58 logMar, SD = 0.30 vs 0.73 logMar, SD = 0.41; p = 0.0007). Patients then showed a further significant improvement in visual acuity after switching and receiving a course of ranibizumab (0.51 logMar, SD = 0.32) (p = 0.0122). Mean central retinal thickness as measured by optical coherence tomography significantly decreased after a course of bevacizumab (p = 0.0158), and a further decrease was noted after a subsequent course of ranibizumab (p < 0.0001). CONCLUSIONS: There was a significant improvement in visual acuity and central retinal thickness in patients with neovascular AMD initially treated with bevacizumab. When these patients were uniformly switched to ranibizumab there was a further significant improvement in visual acuity and a reduction of retinal thickness. It appears that ranibizumab can maintain, or improve the effect achieved after an initial course of bevacizumab.

Intravitreal injection anesthesia--comparison of different topical agents: a prospective randomized controlled trial.

PURPOSE: To compare the anesthetic effectiveness of 3 topical agents used for intravitreal injections. DESIGN: Randomized, triple-armed, double-blinded, prospective, single-centered trial in patients receiving intravitreal ranibizumab for neovascular age-related macular degeneration. METHODS: Patients were randomized 1:1:1 to receive 0.5% tetracaine hydrochloride drops and a 4% lidocaine pledget (n = 31), 0.5% tetracaine hydrochloride drops alone (n = 31), or 4% cocaine (+ epinephrine 1/100,000) drops alone (n = 31). Patients were asked to score their pain experience using a visual analogue scale (VAS) immediately following and 15 minutes after their injection. The average of these scores was used as the primary outcome. The physician performing the procedure separately scored his perception of the patients' pain using the Wong-Baker FACES scale. RESULTS: Means of the averaged VAS pain score for Groups 1, 2, and 3 were: 19 (95% confidence interval [CI] 12-26), 21 (95% CI 13-29), and 21 (95% CI 16-27) respectively. Mean Wong-Baker pain scores for Groups 1, 2, and 3 were 1.9 (95% CI 1.3-2.6), 2.1 (95% CI 1.4-2.7), and 2.3 (95% CI 1.6-3.1) respectively. There was no significant difference (P = .549) between groups for average VAS pain score. Similarly, there was no significant difference (P = .790) for the physician-perceived pain score between groups. CONCLUSIONS: There was no clinical difference in patient pain experience between the 3 anesthetic options tested. The addition of a 4% lidocaine pledget offered no clinical advantage in pain relief compared to 0.5% tetracaine or 4% cocaine (+ epinephrine 1/100,000) drops alone.

The role of Frizzled-4 mutations in familial exudative vitreoretinopathy and Coats disease.

AIM: The aim of this study is to assess the role of Frizzled-4 (FZD4) in familial exudative vitreoretinopathy (FEVR) and Coats disease. METHODS: Tissue samples were collected for DNA extraction and automated DNA sequencing of the two coding exons of FZD4 in both directions. Cases carrying a FZD4 mutation and demonstrating extreme disease severity were selected for direct automated sequencing of all coding exons of LRP5, NDP and TSPAN12. Clinical data were obtained for the purpose of identifying genotype-phenotype correlations. RESULTS: 68 probands were diagnosed as having autosomal dominant or sporadic FEVR. Eleven FZD4 mutations (five missense, three deletions, one insertion, two nonsense) were identified. Six of these mutations are novel, and none were found in 346 control chromosomes. In 16 cases of Coats disease, one polymorphism combination was found in two samples: no mutations were detected. No genotype-phenotype correlation emerged. Three severely affected cases with FZD4 mutations failed to show additional mutations in the three other FEVR genes. CONCLUSION: The authors identified 12 FEVR probands with FZD4 mutations. FZD4 mutation screening can be a useful tool especially in mild or atypical cases of FEVR. Germ-line mutations in FZD4 do not appear to be a common cause of Coats disease.

Combination therapy in exudative age-related macular degeneration: visual outcomes following combined treatment with photodynamic therapy and intravitreal bevacizumab.

OBJECTIVE: To measure visual outcomes following combined treatment with photodynamic therapy (PDT) and intravitreal bevacizumab for exudative age-related macular degeneration (AMD). DESIGN: Single-centre, retrospective cohort analysis. PARTICIPANTS: One hundred and seventy-four eyes in 174 patients, representing a consecutive series of all patients with at least 6 months' follow-up after combined treatment with PDT and bevacizumab for exudative AMD. METHODS: Each patient was treated with PDT, followed by intravitreal injection of bevacizumab approximately 30 minutes later. The patients were then followed at 8-12-week intervals. The primary outcome of the study was the mean change in visual acuity (VA) from baseline. RESULTS: One hundred seventy-four eyes in 174 patients completed at least 6 months' follow-up, with a mean duration of 10 months. The mean number of treatments was 3.0 for bevacizumab and 1.4 for PDT. After stabilization, the mean treatment-free interval was 193 days, and 52% of the patients did not require postinduction retreatment. Mean VA improved from baseline at 2, 4, and 6 months of follow-up (p < 0.05). In the subgroup analysis, treatment-naïve patients had more favorable visual outcomes (p < 0.05). CONCLUSIONS: The combination of PDT and intravitreal bevacizumab is an effective therapy for preserving VA in patients with exudative AMD.