Long-Term Evaluation of Pseudoexfoliation Syndrome Post-Cataract Extraction.

The study aimed to examine the effect of cataract extraction on ophthalmologists' ability to detect pseudoexfoliation (PXF) syndrome. A total of 31 patients admitted for elective cataract surgery were enrolled in this prospective comparative study. Prior to surgery, patients underwent slit-lamp examination and gonioscopy conducted by experienced glaucoma specialists. Subsequently, patients were re-examined by a different glaucoma specialist and comprehensive ophthalmologists. Pre-operatively, 12 patients were diagnosed with PXF on the basis of a Sampaolesi line (100%), anterior capsular deposits (83%), and pupillary ruff deposits (50%). The remaining 19 patients acted as controls. All patients were re-examined 10-46 months post-operatively. Of the 12 patients with PXF, 10 (83%) were correctly diagnosed post-operatively by glaucoma specialists and 8 (66%) by comprehensive ophthalmologists. There was no statistically significant difference in PXF diagnosis. However, detection of anterior capsular deposits (p = 0.02), Sampaolesi lines (p = 0.04), and pupillary ruff deposits (p = 0.01) were significantly lower post-operatively. Diagnosis of PXF is challenging in pseudophakic patients as the anterior capsule is removed during cataract extraction. Therefore, PXF diagnosis in pseudophakic patients relies mainly on the presence of deposits at other anatomical sites, and careful attention to these signs is required. Glaucoma specialists may be more likely than comprehensive ophthalmologists to detect PXF in pseudophakic patients.

Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study).

OBJECTIVE: To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD). DESIGN: Multicenter, open-label, prospective, randomized, comparator-controlled exploratory study. PARTICIPANTS: A total of 151 patients with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD who were naive to AMD therapy. METHODS: In this phase 2 study, patients were randomized to 1 of 5 treatment groups with equal ratio. All groups received ranibizumab 0.5 mg at baseline and (a) PF 1 mg every 4 weeks (Q4W) from week 4 to week 12; (b) PF 3 mg Q4W from week 4 to week 12; (c) PF 3 mg every 2 weeks (Q2W) from week 4 to week 12; (d) PF 1 mg + ranibizumab (combination) Q4W from baseline to week 12; and (e) ranibizumab Q4W to week 12. All study treatments were given as intravitreal injections. MAIN OUTCOME MEASURES: The primary end point was the mean change in best-corrected visual acuity (BCVA) from baseline at week 16; secondary end points included the percentage of patients gaining ≥ 10 and ≥ 15 letters in BCVA and mean change in retinal central subfield thickness, lesion thickness, and CNV area. RESULTS: At week 16, the PF 1 mg + ranibizumab combination group achieved numerically greater improvement in mean BCVA from baseline (9.5 letters) than the ranibizumab group (6.8 letters). The difference was not statistically significant. The BCVA improvement in the PF monotherapy groups was less than in the ranibizumab group. Similar trends were observed in the percentage of patients who gained ≥ 10 and ≥ 15 letters. From baseline to week 16 (last observed carried forward), the combination and ranibizumab groups had similar mean reductions in central subfield retinal thickness and total CNV area, which were greater than in all PF monotherapy groups. There were no clinically meaningful differences in reduction of lesion thickness among treatment groups. CONCLUSIONS: In this early, underpowered study evaluating treatments for neovascular AMD, the combination of PF with ranibizumab led to an average gain in BCVA that was more than with ranibizumab monotherapy. No safety concerns were identified.

Cost containment by peer prior authorization program for second line treatment in patients with retinal disease.

BACKGROUND: High and increasing drug prices have prompted the establishment of a broad range of cost-containment treatment policies in health systems globally. In 2012, the supplemental insurance program of a large Israeli health maintenance organization (Clalit Health Services) introduced a prior authorization process for second-line use of ranibizumab in patients with retinal disease for whom treatment with bevacizumab proved to be ineffective. A Clalit steering committee established authorization criteria based on cost and periodically updated clinical considerations, while a team of ophthalmic specialists evaluated their colleagues' individual patient subsidization requests, based on the funding criteria. The objectives of this study were to detail this unique authorization process and study its effectiveness in limiting unwarranted spending, while allowing for a smooth transition to a second-line more expensive drug when needed. METHODS: A retrospective cohort study including all applications for a first or ongoing treatment with ranibizumab, for one or both eyes, received during March 1, 2012 - December 31, 2015. The key parameters examined were percentages of requests from patients treated by first line treatment bevacizumab, requests approved, reapplications, and results. Requests studied include reapplications and requests for treatment continuation. RESULTS: During the study period, Clalit affiliated ophthalmologists' submitted 16,778 funding applications for intravitreal ranibizumab treatment on behalf of 5642 patients who applied for approximately three applications. An efficient sentinel effect was achieved, resulting in only 31% of patients treated with bevacizumab applying for treatment, while maintaining extremely high accessibility to second line treatment with almost 95% of requests being approved. CONCLUSIONS: The data presented shows a low request rate for funding with a high approval rate, proving this peer reviewed report-based authorization process successfully achieved a sentinel effect while controlling cost. We suggest this innovative model be considered in similar decisions processes.

Photodynamic therapy for choroidal neovascularization in young adult patients.

We report our experience with photodynamic therapy (PDT) in the treatment of choroidal neovascularization (CNV) in young adult patients. This was a retrospective study of young adults with CNV treated with PDT. Data collected included age, diagnosis, type and size of CNV, number of treatments, visual outcome, and side effects. Ten patients (11 eyes) were included in the study (mean age 27.2 +/- 13.3 years). Etiologies included multifocal choroiditis (3 eyes), idiopathic CNV (5 eyes), central serous chorioretinopathy (1 eye), and toxoplasma (2 eye). The mean number of treatments was 2 +/- 0.7 and the mean follow-up time was 13.1 +/- 9.5 months. Initial visual acuity (VA) ranged from 20/25 to 20/1,200 (mean logMAR 0.6 +/- 0.5), and improved to 20/20 to 20/250 (mean logMAR 0.46 +/- 0.4) (P = 0.51). Of the four eyes that received additional treatment with oral steroids, one of which also received intravitreal bevacizumab (Avastin) injections, all had visual acuity improvement of 2 or more lines, while only two of seven eyes that received PDT alone showed such improvement. PDT can improve visual outcome in a subgroup of young patients with subfoveal CNV especially when supplemented with oral steroid and bevacizumab injections.

Multimodal Imaging in an Unusual Cluster of Multiple Evanescent White Dot Syndrome.

OBJECTIVE: To describe an unusual cluster of multiple evanescent white dot syndrome (MEWDS) encountered within a 3-month period. METHODS: This retrospective observation study is comprised of seven patients who presented with MEWDS in a 3-month period in central Israel. Data were collected from patients' medical records on clinical, multimodal imaging, and viral serology findings. RESULTS: Six women and one man of mean age 31.5 ± 7.2 years. Three reported a precedent viral infection. All had unilateral decreased vision. Funduscopy revealed foveal granularity. MAIN IMAGING FINDINGS: Hyperfluorescent spots on blue autofluorescence (BAF), hypofluorescent spots on indocyanine green angiography, dark lesions on infrared photos, and ellipsoid zone irregularities on spectral domain optical coherence tomography (SD-OCT). Resolution of the spots on BAF correlated with anatomic (SD-OCT) and visual recovery. OCT angiography performed following the convalescence stage demonstrated intact retinal and choroidal flow. Serologic findings were inconclusive. CONCLUSION: We report a unique cluster of MEWDS patients presented in a short period of time. SD-OCT findings of ellipsoid zone disruption in combination with other multimodal imaging modalities are outlined meticulously. Recognizing these imaging features along with high index of clinical suspicion is important for the diagnosis of MEWDS. Serologic testing might be considered in future patients.

Combined pars plana vitrectomy and cataract surgery: outcome of phacoemulsification versus manual extracapsular cataract extraction through a sclerocorneal tunnel.

BACKGROUND AND OBJECTIVE: To compare the results of combined pars plana vitrectomy and cataract extraction with intraocular lens implantation by phacoemulsification versus manual extracapsular cataract extraction through a sclerocorneal tunnel. PATIENTS AND METHODS: Retrospective chart review of all patients who underwent combined pars plana vitrectomy with intraocular lens implantation and phacoemulsification or extracapsular cataract extraction through a sclerocorneal tunnel between March 1992 and July 2002. RESULTS: Fifty-four eyes of 51 patients were evaluated. Mean age was 69.68 +/- 9.11 years, and mean follow-up was 9 months. Phacoemulsification was performed in 35 cases (64%) and manual extraction in 19 cases (36%). Visual acuity improved from mean logarithm of the minimal angle of resolution 1.69 +/- 0.54 before surgery to 1.22 +/- 0.76 after surgery. There was a greater improvement of visual acuity in the phacoemulsification group (0.59 +/- 0.67) than in the extracapsular cataract extraction group (0.22 +/- 0.68) (P = .06). Final visual acuity was correlated to the vitreoretinal pathology. Ultrasound biomicroscopy showed well-positioned foldable or rigid intraocular lens in the bag or in the sulcus. CONCLUSION: Combined cataract extraction by phacoemulsification or extracapsular cataract extraction through sclerocorneal tunnel and pars plana vitrectomy are safe and effective procedures.

Combined photodynamic therapy and intravitreal triamcinolone acetonide injection for neovascular age-related macular degeneration with pigment epithelium detachment.

BACKGROUND AND OBJECTIVE: To report the outcome of combined verteporfin photodynamic therapy (PDT) and intravitreal triamcinolone acetonide (IVTA) for the treatment of choroidal neovascularization (CNV) with serous pigment epithelium detachment (PED) due to age-related macular degeneration (AMD). PATIENTS AND METHODS: The files of all consecutive patients with CNV and serous PED who received PDT and IVTA either primarily (primary treatment group) or following previous unsuccessful PDT (secondary treatment group) were reviewed for visual and angiographic results. RESULTS: Ten patients (11 eyes) were included. Mean number of PDT sessions was 3.18; 8 eyes received one IVTA injection and 3 eyes received two IVTA injections. Thirty-six percent of patients retained their initial visual acuity after a mean follow-up of 15.3 months. Loss of 3 or more Snellen lines was noted in 2 of 3 eyes in the primary treatment group and 5 of 8 eyes in the secondary treatment group. Increased intraocular pressure developed in 3 patients and was controlled by topical medications. CONCLUSIONS: Although combined PDT and IVTA may be considered for CNV with serous PED in patients with poor prognosis with PDT alone, the regimen as administered in this small series was not beneficial. Further studies are required to determine whether alternate sequences, timing, or doses would yield a better outcome.

Ischemic optic neuropathy in dialyzed patients: a previously unrecognized manifestation of calcific uremic arteriolopathy.

Two patients with end-stage renal disease and on long-term hemodialysis presented with hypotension and an acute unilateral loss of vision. A diagnosis of anterior ischemic optic neuropathy (AION) was made quickly, but despite high-dose steroid therapy, significant vision was not recovered. Temporal artery biopsy results showed extensive medial calcification. The possibility that hypotension, when coupled with calcific uremic arteriolopathy in arteries supplying the optic nerve head, will lead to AION in dialyzed patients is discussed. A short review of AION in the dialysis population is given.

Photodynamic therapy for occult choroidal neovascularization with pigment epithelium detachment in age-related macular degeneration.

OBJECTIVE: To study the visual and angiographic outcome of eyes with neovascular age-related macular degeneration associated with pigment epithelium detachment (PED) treated by photodynamic therapy. METHODS: Review of the medical charts and the fluorescein and indocyanine green angiograms of all consecutive patients with age-related macular degeneration associated with choroidal neovascularization and serous PED of at least 1 disc diameter, who received photodynamic therapy from January 1, 2000, to August 31, 2002. RESULTS: Thirty patients (34 eyes) met the study criteria. Each underwent 1 to 8 treatments (mean, 4); duration of follow-up was 12 to 36 months (mean, 19 months). Nineteen eyes (56%) lost 3 or more Snellen lines of visual acuity, 7 eyes (21%) lost 1 or 2 lines, 6 eyes (18%) maintained their initial acuity, and 2 eyes (6%) gained 1 or 2 lines. Subretinal hemorrhage occurred in 5 eyes and retinal pigment epithelium tears in 4 eyes. In 4 eyes, visual acuity decreased to counting fingers, hand motions, or light perception. CONCLUSIONS: Although 44% of the 34 eyes with age-related macular degeneration and PED lost fewer than 3 Snellen lines in acuity, severe visual loss to counting fingers or less occurred in 4 eyes, 3 of them with choroidal neovascularization inside the PED. Further studies and treatment modalities are required to improve prognosis of neovascular age-related macular degeneration with serous PED.

Photodynamic therapy of subfoveal choroidal neovascularization in high myopia in a clinical setting: visual outcome in relation to age at treatment.

PURPOSE: To evaluate the visual outcome of patients with myopic subfoveal choroidal neovascularization (CNV) given photodynamic therapy (PDT) in a clinical setting, and to identify potential relation between the visual outcome and the age at treatment. DESIGN: Interventional case series. METHODS: Retrospective comparative study. SETTING: Outpatient ophthalmology clinic. PATIENTS: Twenty-nine consecutive patients (30 eyes) with subfoveal CNV caused by pathologic myopia who were treated with verteporfin PDT from January 2000 to May 2003. INTERVENTION: All the patients received verteporfin PDT and were followed clinically and with fluorescein angiography (FA). Review of the medical records and angiograms was performed. Patients were divided into two groups by age, using the median age (60 years) as the cutoff. MAIN OUTCOME MEASURES: Visual acuity (VA) at the end of follow-up in the older-patient group compared with the younger-patient group. RESULTS: The mean age was 63.1 years. Mean follow-up was 11.5 months. Patients received a mean of 3.48 treatments. Mean VA improved in the younger group from 0.63 to 0.39 logMAR (P = .02, paired t test) and deteriorated in the older group from 0.71 to 0.99 logMAR (P = .03, paired t test). In the whole cohort, 33% of eyes lost 3 or more lines of Snellen best-corrected VA; in the older age group, 50% of eyes lost 3 or more lines, whereas in the younger age group, only 8% of eyes did so (P = .024, Fisher's exact test). CONCLUSIONS: In our consecutive case series, visual prognosis of myopic CNV after PDT was found to be influenced by age at treatment.

Photodynamic therapy for age-related macular degeneration in a clinical setting: visual results and angiographic patterns.

PURPOSE: To evaluate the visual outcome of patients with subfoveal choroidal neovascularization due to age-related macular degeneration, who received photodynamic therapy (PTD) in a clinical setting and to identify potential predictive visual and angiographic factors. DESIGN: Interventional case series. METHODS: The study included 74 patients with subfoveal choroidal neovascularization who underwent PDT from January 2000 to March 2001 and completed at least 1 year follow-up. All patients received verteporfin PDT and were followed clinically, with fluorescein angiography (74 eyes), and with indocyanine green angiography (65 eyes). A review of the medical records and angiograms was performed. RESULTS: Mean follow-up was 15.6 months. Patients received a mean of 3.4 treatments per year. Sixty-six percent lost less than 3 Snellen lines of visual acuity. Three patients (4%) experienced profound visual acuity loss to finger counting. Final visual acuity was positively correlated with lesion size and visual acuity at presentation. Visual outcome was worse in the presence of cystoid macular edema. On indocyanine green angiography, a round hypofluorescent spot was seen at the site of the PDT, with maintenance of medium and large choroidal vessels. CONCLUSION: Smaller lesion size and better visual acuity at presentation were good predictive signs, whereas cystoid macular edema was found to be a poor prognostic sign for visual outcome following PDT.

Interferon alpha-2a for proliferative diabetic retinopathy after complete laser panretinal photocoagulation treatment.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the effect of interferon alpha-2a, an angiogenesis inhibitor, on eyes with active neovascularization after complete laser panretinal photocoagulation treatment. PATIENTS AND METHODS: Eight patients with active neovascularization persisting for 6 months or more after completion of full panretinal photocoagulation were included in the study. All patients were treated with subcutaneous injections of 6 million international units of interferon alpha-2a, 3 times a week, for an average period of 10 months. Visual acuity, contrast sensitivity, blood tests, fundus photographs, fluorescein angiography, and physical examination were performed periodically. The main outcome measures were visual acuity and extent of neovascularization as assessed by fundus photography and fluorescein angiography. RESULTS: The 5 men and 3 women (mean age, 60 years) had a mean duration of diabetes of 19 years. The average study follow-up was 42.2 +/- 8.7 weeks. Visual acuity and extent of neovascularization improved or remained stable in 7 patients. In none of the patients was there progression of neovascularization, but in 1 patient it could not be assessed due to vitreous hemorrhage. Most patients had malaise during the first weeks of treatment, but none of the patients suffered from nonreversible side effects associated with interferon alpha-2a. CONCLUSION: This pilot study provides evidence that interferon alpha-2a might have a role in the regression of proliferative diabetic retinopathy and that further investigation is warranted.

Indocyanine green angiography in high myopia.

BACKGROUND AND OBJECTIVE: To evaluate indocyanine green imaging of choroidal changes in pathologic myopia and to compare it with fluorescein angiography. PATIENTS AND METHODS: The angiograms of all consecutive patients with pathologic myopia photographed with confocal indocyanine green angiography using a scanning infrared laser or ophthalmoscope from March 1997 to December 1999 were reviewed. RESULTS: Twenty-one patients (35 eyes) were included. Indocyanine green angiography was performed in 35 eyes and immediate sequential fluorescein angiography and indocyanine green angiography in 25 eyes. The lacquer cracks were demonstrated to radiate from the disc, at the papillomacular bundle, through the macula, and around the macula. Lacquer cracks were identified in 89% and 28% of the eyes, respectively. Choroidal neovascularization (CNV) was demonstrated in 57% of eyes by indocyanine green angiography and in 56% by fluorescein angiography. All of the CNVs were classic and were located within 300 microm of the foveal center. Seventy percent of the CNVs were delineated in lacquer cracks by indocyanine green angiography. Overall, 124 lacquer cracks were identified by indocyanine green angiography and only 14 by fluorescein angiography. Lipids or serous detachment were not observed. Retinal hemorrhages were noted in 22% and 28% of eyes with indocyanine green angiography and fluorescein angiography, respectively. CONCLUSION: Confocal indocyanine green angiography offers better delineation of lacquer cracks and the localization of the CNV in lacquer cracks than does fluorescein angiography.

Dose-ranging evaluation of intravitreal siRNA PF-04523655 for diabetic macular edema (the DEGAS study).

PURPOSE: To evaluate the safety and efficacy of three doses of PF-04523655, a 19-nucleotide methylated double stranded siRNA targeting the RTP801 gene, for the treatment of diabetic macular edema (DME) compared to focal/grid laser photocoagulation. METHODS: This multicenter, prospective, masked, randomized, active-controlled, phase 2 interventional clinical trial enrolled 184 DME patients with best corrected visual acuity (BCVA) of 20/40 to 20/320 inclusive in the study eye. Patients were randomly assigned to 0.4-mg, 1-mg, 3-mg PF-04523655 intravitreal injections or laser. The main outcome measure was the change in BCVA from baseline to month 12. RESULTS: All doses of PF-04523655 improved BCVA from baseline through month 12. At month 12, the PF-04523655 3-mg group showed a trend for greater improvement in BCVA from baseline than laser (respectively 5.77 vs. 2.39 letters; P = 0.08; 2-sided α = 0.10). The study was terminated early at month 12 based on predetermined futility criteria for efficacy and discontinuation rates. PF-04523655 was generally safe and well-tolerated, with few adverse events considered treatment-related. By month 12, the discontinuation rates in the PF-04523655 groups were higher than the laser group and were inversely related to dose levels. CONCLUSIONS: PF-04523655 showed a dose-related tendency for improvement in BCVA in DME patients. Studies of higher doses are planned to determine the optimal efficacious dose of PF-04523655. PF-04523655 may offer a new mode of therapeutic action in the management of DME. (ClinicalTrials.gov number, NCT00701181.).

Pneumatic displacement of submacular hemorrhage due to age-related macular degeneration.

PURPOSE: Subretinal hemorrhage is one of the most serious complications of exudative age-related macular degeneration (AMD). Treatment with vitreous surgery with or without plasminogen activator, fluid-gas exchange, or perfluorocarbon yields only a small improvement in visual acuity. PATIENTS AND METHODS: The files of 24 patients with submacular hemorrhage secondary to AMD who were treated by injection of perfluoropropane gas (C(3)F(8)) (11 patients) or sulfur hexafluoride (SF(6)) (13 patients) were reviewed for visual acuity before and after the procedure and time of treatment from onset of symptoms. RESULTS: For the whole sample, pneumatic displacement led to a statistically significant improvement in mean visual acuity (p = 0.015). A significant difference between pre- and postoperative visual acuity was found for the patients treated with SF(6) (p = 0.034), but not for the patients treated with C(3)F(8) (p = 0.245). CONCLUSION: The use of gas injection to displace submacular hemorrhage can significantly improve visual acuity.