Mitsuko Yuzawa

The origins of polypoidal choroidal vasculopathy.

Background/aim: There are two theories on the pathogenesis of polypoidal choroidal vasculopathy (PCV): variants in choroidal neovascularisation (CNV) and inner choroidal vessel abnormalities. On indocyanine green angiography (IGA) with a video camera system, PCV has a characteristic appearance, but inadequate image quality has made detailed interpretation difficult. This study aims to improve imaging, using confocal scanning laser ophthalmoscopy (SLO), to elucidate the pathogenesis of PCV. Methods: High speed IGA with confocal SLO of 45 eyes (44 patients) showed typical PCV findings of a branching vascular network and polypoidal lesions. Results: Vessels comprising branching networks began to fill simultaneously with the surrounding choroidal arteries in 38 eyes. Small numbers of vessels filling within a branching network, in the arterial and arteriovenous phases of IGA, showed focal dilatation, constriction, and tortuousity. Vessel abnormalities, corresponding to polypoidal lesions, existed within a network in eight eyes and included loops similar in calibre to network vessels, and numerous microaneurysmal dilatations of small vessels. Vessel pulsation was seen in 24 eyes. Conclusion: PCV is caused by inner choroidal vessel abnormalities, not CNV.

Clinicopathologic Findings in Polypoidal Choroidal Vasculopathy

PURPOSE To elucidate the pathogenic mechanism of polypoidal choroidal vasculopathy (PCV) based on histopathologic findings. METHODS Specimens obtained by surgical excision of PCV from five eyes of five patients (mean age, 75.6 +/- 3.1 years) were studied histopathologically. Immunohistochemical studies were also performed to identify CD34, vascular endothelial growth factor (VEGF), CD68, alpha-smooth muscle actin (alpha-SMA) and hypoxia-inducible factor (HIF)-1alpha. RESULTS Hyalinization of choroidal vessels and massive exudation of fibrin and blood plasma were observed in all the specimens of PCV lesions. Some blood vessels were located above the RPE in two of the five eyes. Immunohistochemically, CD68-positive cells were detected around the hyalinized vessels. There were no alpha-SMA-positive cells in the vessels of PCV. CD34 staining showed endothelial discontinuity. Vascular endothelial cells within the PCV specimens were negative for VEGF. HIF-1alpha positive inflammatory cells were located in the stroma of specimens. CONCLUSIONS Hyalinization of choroidal vessels, like arteriosclerosis, is characteristic of PCV.

Polypoidal choroidal vasculopathy: evidence-based guidelines for clinical diagnosis and treatment.

Background: Polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy affecting vision, with clinical features distinct from neovascular age-related macular degeneration. Currently, no evidence-based guidelines exist for its diagnosis and treatment. Methods: A panel of experts analyzed a systematic literature search on PCV together with results of the EVEREST trial, the only published randomized controlled clinical trial in PCV. At a subsequent Roundtable meeting, recommendations for the management of PCV were agreed based on this analysis and their own expert opinion. Results: Diagnosis of PCV should be based on early-phase nodular hyperfluorescence from choroidal vasculature visualized using indocyanine green angiography. Recommended initial treatment of juxtafoveal and subfoveal PCV is either indocyanine green angiography-guided verteporfin photodynamic therapy or verteporfin photodynamic therapy plus 3 × 0.5 mg ranibizumab intravitreal injections 1 month apart. If there is incomplete regression of polyps by indocyanine green angiography, eyes should be retreated with verteporfin photodynamic therapy monotherapy or verteporfin photodynamic therapy plus ranibizumab. If there is complete regression of polyps by indocyanine green angiography, but there is leakage on fluorescein angiography and other clinical or anatomical signs of disease activity, eyes should be retreated with ranibizumab. Conclusion: Practical guidance on the clinical management of PCV is proposed based on expert evaluation of current evidence.

Psychometric properties of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), Japanese version.

BackgroundThe importance of evaluating the outcomes of health care from the standpoint of the patient is now widely recognized. The purpose of this study is to develop and test a Japanese version of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25).MethodsA Japanese version was developed with a previously standardized method. The questionnaire and optional items were completed by 245 patients with cataracts, glaucoma, or age-related macular degeneration, by 110 others before and after cataract surgery, and by a reference group (n = 31). We computed rates of missing data, measured reproducibility and internal consistency reliability, and tested for convergent and discriminant validity, concurrent validity, known-groups validity, factor structure, and responsiveness to change.ResultsBased on information from the participants, some items were changed to 2-step items (asking if an activity was done, and if it was done, then asking how difficult it was). The near-vision and distance-vision subscales each had 1 item that was endorsed by very few participants, so these items were replaced with items that were optional in the English version. For example, more than 60% of participants did not drive, so the driving question was excluded. Reliability and validity were adequate for all subscales except driving, ocular pain, color vision, and peripheral vision. With cataract surgery, most scores improved by at least 20 points.ConclusionWith minor modifications from the English version, the Japanese NEI VFQ-25 can give reliable, valid, responsive data on vision-related quality of life, for group-level comparisons or for tracking therapeutic outcomes.

Long-term results of photodynamic therapy of polypoidal choroidal vasculopathy.

Purpose: This study evaluated the results of photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV) 24 months or more after treatment. Methods: The study involved 47 eyes of 47 patients with PCV followed for 24 months or more after the first PDT. Fundus appearance, indocyanine green angiographic findings, and visual acuity (VA) were compared before PDT, and then at 3 months, 12 months, and the final visit after the first PDT. Results: At the final visit, VA was preserved or improved in 37 (79%) of the 47 eyes. Recurrence of polypoidal lesions was noted in 30 eyes (64%). An abnormal branching vascular network persisted in all subjects. In 26 of the 30 eyes exhibited recurrence of polypoidal lesions, which appeared in the periphery of the expanded abnormal branching vascular network. Conclusion: Patients with PCV need to be followed for long periods of time after PDT because of the high incidence of polypoidal lesion recurrence. However, since polypoidal lesions often recur outside the fovea, and thus have little effect on VA, PDT can be expected to exert long-term efficacy in treating PCV.

Incidence of Endophthalmitis after 20- and 25-Gauge Vitrectomy: Causes and Prevention

PURPOSE To compare endophthalmitis incidence after inpatient 20-gauge (20-G) and 25-G vitrectomies, and to examine the causes and prevention of postvitrectomy endophthalmitis. DESIGN Retrospective, interventional, comparative cohort study. PARTICIPANTS Six thousand nine hundred thirty-five consecutive patients undergoing pars plana vitrectomy. METHODS We compared the incidence of endophthalmitis in 3592 consecutive eyes that underwent 20-G vitrectomy between January 2000 and September 2004, and 3343 consecutive eyes that underwent 25-G vitrectomy between April 2004 and December 2007. For 25-G vitrectomy, 542 eyes with sclerotomies produced by straight incision and 2801 eyes with angled incisions were also compared. From 85 eyes that underwent 20-G vitrectomy and 128 eyes that underwent 25-G vitrectomy, ocular surface irrigation fluid and vitreous samples were collected at the end of surgery for bacterial culture. MAIN OUTCOME MEASURES Incidence of postvitrectomy endophthalmitis. RESULTS The incidence of postoperative endophthalmitis was 0.0278% (1 of 3592 eyes) for 20-G vitrectomies and 0.0299% (1 of 3343 eyes) for 25-G vitrectomies, with no significant difference. Two eyes developed endophthalmitis after vitrectomy, and visual acuity deteriorated to no light perception despite emergency vitreous surgery. The causative bacteria were methicillin-resistant Staphylococcus aureus and Enterococcus faecali; both were resistant to postoperative antibiotics. In 25-G vitrectomy, the endophthalmitis incidence was 0.18% (1/542 eyes) for straight incision versus 0% (0/2801 eyes) for angled incision, with no significant difference (P = 0.1621). Bacterial contamination rates in ocular surface irrigation fluid and the vitreous were 5.9% (5/85 eyes) and 1.2% (1/85 eyes), respectively, in 20-G vitrectomies, and 5.5% (7/128 eyes) and 2.3% (3/128 eyes) in 25-G vitrectomies, with no significant difference. CONCLUSIONS The incidence of endophthalmitis was 0.03% for both 20-G and 25-G vitrectomies. This is the first data set to demonstrate no statistically significant difference between endophthalmitis rates in 20-G and 25-G vitrectomy. At the completion of 25-G vitrectomy, the ocular surface irrigation fluid and vitreous were, on rare occasion, contaminated by antibiotic-resistant bacteria. In 25-G vitrectomy, conjunctival irrigation, ensuring sclerotomy closure, and excision of peripheral vitreous may contribute to the prevention of postvitrectomy endophthalmitis. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any materials discussed in this article.

Double staining with brilliant blue G and double peeling for epiretinal membranes.

PURPOSE To compare methods of removing epiretinal membranes (ERM) and evaluate the usefulness of the double brilliant blue G (BBG) staining and double-peeling method. DESIGN Prospective, interventional case series. PARTICIPANTS We followed 246 consecutive patients who underwent pars plana vitrectomy to remove ERM and for > or =12 months. METHODS Of the 246 eyes, 104 underwent single ERM peeling using indocyanine green staining, and 142 underwent ERM peeling by 1 of the 3 following methods: without staining in 46 eyes, triamcinolone acetonide staining in 42, and BBG staining in 54. Peeling of residual internal limiting membrane (ILM) was then conducted using BBG. In the latter group, the ILM that remained after the initial peeling procedure was evaluated macroscopically with BBG staining and also histopathologically. In 6 eyes requiring reoperation owing to ERM recurrence, the peeled ERM was examined histopathologically. MAIN OUTCOME MEASURES Postoperative visual acuity and recurrence of ERM. RESULTS The ERM recurrence rate was 16.3% (17 eyes) and the reoperation rate was 5.8% (6 eyes) among the 104 eyes that underwent single ERM peeling, compared with 0% in 142 eyes with double ERM and ILM peeling. Although the ERM recurrence rate was significantly lower with double peeling, postoperative visual acuity did not differ between the 2 methods. The 3 ERM peeling methods differed in the rate and extent of residual ILM, and the lowest rate (21/54 eyes; 39%) was achieved with BBG staining (P<0.0001). Histopathologic examination of the ILM remaining after ERM peeling detected remnant ERM cells on the ILM. Histopathologic examination of the peeled ERM in 6 eyes with ERM recurrence showed residual ILM to serve as a scaffold for cell proliferation. CONCLUSIONS This study verified that ERM recurrence arises from remnant ERM components on the ILM, which proliferate using the ILM as a scaffold, and that complete ILM removal seems to reduce the risk of recurrence. Brilliant blue G with good affinity for the ILM facilitates simultaneous ERM and ILM peeling in many cases, and BBG contact with the retina in the second staining has no apparent effect on visual acuity. Double BBG staining and double peeling is useful for ERM treatment.

Role of Photodynamic Therapy in Polypoidal Choroidal Vasculopathy

PurposeTo determine the efficacy of photodynamic therapy (PDT) with verteporfin for polypoidal choroidal vasculopathy (PCV).MethodsPDT was performed in 35 patients (35 eyes) with PCV. We evaluated the number of treatments and compared visual acuity (VA), ophthalmological findings, and changes in polypoidal lesions and branching vascular networks by measuring lesion diameters using Heidelberg retina angiography before PDT, and then every 3 months for 1 year after PDT.ResultsThe mean annual number of treatment sessions was 2.2. VA was improved or maintained in 80% of the patients. Retinal pigment epithelium detachment, retinal detachment, hemorrhage, and/or exudates disappeared in 69%, and leakage resolved in 74% of the patients. Polypoidal lesions disappeared completely on indocyanine green angiography in 83% of the patients. All branching vascular networks persisted. Polypoidal lesions had recurred at the termini of the remaining branching vascular networks at 9 months after the first PDT in two eyes and at 12 months in one eye.ConclusionsPDT with verteporfin for PCV appears to improve or maintain VA for the first posttreatment year. Approximately 70% of PCV cases showed improved ophthalmoscopic findings. However, as polypoidal lesions recur after PDT in some cases, further study is needed to confirm the long-term efficacy of PDT for PCV. Jpn J Ophthalmol 2007;51:270–277 @ Japanese Ophthalmological Society 2007

A Study of Laser Photocoagulation for Polypoidal Choroidal Vasculopathy

PURPOSE To evaluate the efficacy of laser photocoagulation for polypoidal choroidal vasculopathy (PCV) involving the macula. METHODS The records of 38 patients (47 eyes) undergoing laser photocoagulation for PCV causing serosanguineous detachment involving the fovea were reviewed and the results were evaluated. Ten eyes underwent photocoagulation to induce a fusion scar covering whole lesions consisting of both abnormal vessels and polypoidal lesions. Thirty-seven eyes underwent photocoagulation for only polypoidal lesions. When serosanguineous detachment recurred, additional photocoagulation was performed, targeting the causative lesions. Photocoagulation was performed with an argon dye laser or multicolor krypton laser. Final visual acuity, macular changes at the final visit, and the number of photocoagulations were evaluated. Follow-up period after the first photocoagulation was at least 1 year. RESULTS Of the 10 eyes undergoing photocoagulation of whole lesions, 9 showed absorption of exudate and/or blood after one photocoagulation, and maintained or improved visual acuity. Of the 37 eyes undergoing laser photocoagulation of only polypoidal lesions, 20 (54%) showed decreased visual acuity because of recurrent or persistent exudation and/or classic choroidal neovascularization or, alternatively, because of atrophy at the fovea; 32 of the 37 eyes had undergone photocoagulation at least twice or more. CONCLUSION Photocoagulation is recommended only for whole lesions.

Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 18-Month Results of the Phase 3 GALILEO Study

PURPOSE To evaluate intravitreal aflibercept for treatment of macular edema secondary to central retinal vein occlusion (CRVO). DESIGN Randomized, double-masked, phase 3 study. METHODS A total of 177 patients with macular edema secondary to CRVO were randomized to receive 2 mg intravitreal aflibercept (n = 106) or sham (n = 71) every 4 weeks for 20 weeks. From weeks 24 to 48, patients were monitored every 4 weeks; the former group received intravitreal aflibercept as needed (PRN), and the sham group received sham. From weeks 52 to 76, patients were monitored every 8 weeks, and both groups received intravitreal aflibercept PRN. The primary endpoint (proportion of patients who gained ≥15 letters) was at week 24. This study reports exploratory outcomes at week 76. RESULTS The proportion of patients who gained ≥15 letters in the intravitreal aflibercept and sham groups was 60.2% vs 22.1% at week 24 (patients discontinued before week 24 were considered nonresponders; P < .0001), 60.2% vs 32.4% at week 52 (last observation carried forward, P < .001), and 57.3% vs 29.4% at week 76 (last observation carried forward; P < .001). Mean μm change from baseline central retinal thickness was -448.6 vs -169.3 at week 24 (P < .0001), -423.5 vs -219.3 at week 52 (P < .0001), and -389.4 vs -306.4 at week 76 (P = .1122). Over 76 weeks, the most common ocular serious adverse event in the intravitreal aflibercept group was macular edema (3.8%). CONCLUSIONS The visual and anatomic improvements seen after fixed, monthly dosing at week 24 were largely maintained when treatment intervals were extended. Patients with macular edema following CRVO benefited from early treatment with intravitreal aflibercept.