Thomas G. Sheidow

Severe retinopathy of prematurity associated with FZD4 mutations

Purpose:u2002To determine whether mutations in the FZD4 gene are a risk factor for developing severe ROP. Methods:u2002Three Canadian tertiary care centers recruited premature infants prospectively and retrospectively, and assigned affectation status based on the maximum degree of severity of ROP recorded in both eyes. Mutation screening of the FZD4 gene was performed using direct sequencing. All sequence changes were evaluated for functional significance. Results:u2002Two novel FZD4 mutations (Ala370Gly or Lys203Asn) were identified in two infants from the severe ROP group (n=71). No mutation was detected in the mild to no ROP group (n=33), and the two novel mutations were absent in 173 random Caucasian samples. Mutation Ala370Gly was also found in one sibling and one parent of the affected infant, but no signs of familial exudative vitreoretinopathy (FEVR), a condition with phenotypic overlap with ROP known to be caused by FZD4 mutations, were present in either family member. Conclusions:u2002Mutations in the FZD4 gene in this group of premature infants supports a role for the FZD4 pathway in the development of severe ROP and accounts for approximately 3% of severe ROP in Caucasian premature infants.

Real-world assessment of intravitreal dexamethasone implant (0.7 mg) in patients with macular edema: the CHROME study.

Background The purpose of this study was to evaluate the real-world use, efficacy, and safety of one or more dexamethasone intravitreal implant(s) 0.7 mg (DEX implant) in patients with macular edema (ME). Methods This was a retrospective cohort study of patients with ME secondary to retinal disease treated at ten Canadian retina practices, including one uveitis center. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), glaucoma and cataract surgery, and safety data were collected from the medical charts of patients with ≥3 months of follow-up after the initial DEX implant. Results One hundred and one patient charts yielded data on 120 study eyes, including diagnoses of diabetic ME (DME) (n=34), retinal vein occlusion (RVO, n=30; branch in 19 and central in 11), and uveitis (n=23). Patients had a mean age of 60.9 years, and 73.3% of the study eyes had ME for a duration of ≥12 months prior to DEX implant injection(s). Baseline mean (± standard error) BCVA was 0.63±0.03 logMAR (20/86 Snellen equivalents) and mean CRT was 474.4±18.2 μm. The mean number of DEX implant injections was 1.7±0.1 in all study eyes; 44.2% of eyes had repeat DEX implant injections (reinjection interval 2.3–4.9 months). The greatest mean peak changes in BCVA lines of vision occurred in study eyes with uveitis (3.3±0.6, P<0.0001), followed by RVO (1.3±0.5, P<0.01) and DME (0.7±0.5, P>0.05). Significant decreases in CRT were observed: −255.6±43.6 μm for uveitis, −190.9±23.5 μm for DME, and −160.7±39.6 μm for RVO (P<0.0001 for all cohorts). IOP increases of ≥10 mmHg occurred in 20.6%, 24.1%, and 22.7% of DME, RVO, and uveitis study eyes, respectively. IOP-lowering medication was initiated in 29.4%, 16.7%, and 8.7% of DME, RVO, and uveitis study eyes, respectively. Glaucoma surgery was performed in 1.7% of all study eyes and cataract surgery in 29.8% of all phakic study eyes receiving DEX implant(s). Conclusion DEX implant(s) alone or combined with other treatments and/or procedures resulted in functional and anatomic improvements in long-standing ME associated with retinal disease.

Canadian expert consensus: optimal treatment of neovascular age-related macular degeneration.

BACKGROUNDnNew therapeutic approaches, particularly anti-vascular endothelial growth factor (anti-VEGF) therapies, prevent, and in some cases reverse, vision damage caused by age-related macular degeneration (AMD). Unequal access to care across Canada remains a problem for many retina specialists and their patients.nnnOBJECTIVEnTo develop a consensus concerning the management of patients with exudative age-related macular degeneration (AMD).nnnDESIGNnConsensus document.nnnPARTICIPANTSnTen Canadian retina specialists.nnnMETHODSnThe development of a consensus among Canadian experts concerning optimal treatment of AMD began with a review of the clinical evidence, daily practices, existing guidelines, and current national and international approvals and policies. The experts met on June 29, 2010, in Quebec City to discuss their findings and to propose strategies for consensus.nnnRESULTSnThe result of this expert panel is a consensus proposal for Canadian ophthalmologists and retina specialists who are treating patients with or at risk for developing neovascular AMD.nnnCONCLUSIONSnThe consensus provides guidelines to aid retina specialists in managing exudative AMD. Currently, ranibizumab is the only agent with sufficient Level I evidence and a Health Canada-approved indication for the treatment of wet AMD. Bevacizumab has been shown to be noninferior in preserving and improving visual acuity when compared to ranibizumab. Potential safety differences between the 2 drugs remain to be elucidated. The positioning of ranibizumab in this therapeutic area will be further defined as additional data for existing and emerging therapies become available. Until then, this agent remains the therapy of choice for individuals with neovascular AMD.

Prospective Evaluation of Teleophthalmology in Screening and Recurrence Monitoring of Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial

IMPORTANCEnTeleophthalmology has the potential to reduce costs and inconveniences associated with frequent patient visits. Evaluating teleophthalmology in the management of age-related macular degeneration (AMD) will allow for future implementation of this technology.nnnOBJECTIVEnTo evaluate teleophthalmology as a tool for the screening and monitoring of neovascular AMD.nnnDESIGN, SETTING, AND PARTICIPANTSnProspective, randomized clinical trial that included 106 referral eyes for suspected neovascular AMD and 63 eyes with stable neovascular AMD. New referrals for patients with suspected neovascular AMD and patients with stable neovascular AMD were randomized into either routine or teleophthalmologic groups. In the routine group, patients received clinical assessment and diagnostic imaging at a tertiary hospital-based retina clinic. In the teleophthalmologic group, patients received basic examination and diagnostic imaging at a stand-alone teleophthalmologic site, where patient information and imaging studies were acquired and electronically sent over to tertiary hospital-based retina specialists. Patients in the teleophthalmologic group were called back to the tertiary treatment center if the teleophthalmologic data set suggested pathology or was inconclusive for diagnosis.nnnMAIN OUTCOMES AND MEASURESnPatient wait times for diagnosis and/or treatment, referral accuracy, and visual outcome.nnnRESULTSnFor neovascular AMD screening, the average referral-to-diagnostic imaging time was 22.5 days for the teleophthalmologic group and 18.0 days for the routine group, for a difference of 4.5 days (95% CI, 11.8 to -2.8 days; Pu2009=u2009.23). The average diagnostic imaging to treatment time was 16.4 days for the teleophthalmologic group and 11.6 days for the routine group, for a difference of 4.8 days (95% CI, 10.7 to -1.1 days; Pu2009=u2009.11). For neovascular AMD monitoring, the average recurrence to treatment time was shorter for the routine group (0.04 days) compared with 13.6 days for the teleophthalmologic group, for a difference of -13.5 days (95% CI, -18.2 to -9.0 days; Pu2009<u2009.01). There was no difference identified between end-of-study visual acuities in the 2 groups (Pu2009=u2009.99).nnnCONCLUSIONS AND RELEVANCEnA delay of referral to treatment time could not be identified when comparing teleophthalmologic screening for suspected neovascular AMD with retinal specialist-based screening. Teleophthalmologic monitoring for neovascular AMD recurrence resulted in longer wait times for treatment reinitiation, but no adverse visual outcomes were identified.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier:NCT01581606.

Intravitreal ranibizumab for the treatment of fibrovascular pigment epithelial detachment in age-related macular degeneration

OBJECTIVEnTo determine the response of predominantly fibrovascular pigment epithelial detachments (PED)-type lesions (secondary to age-related macular degeneration [AMD]) to intravitreal ranibizumab.nnnDESIGNnThis was an open-label prospective study.nnnPARTICIPANTSnThirty-two patients with predominantly fibrovascular PED-type lesions secondary to AMD were included in this study. Three patients were excluded from the final analysis.nnnMETHODSnPatients received monthly intravitreal ranibizumab injections for 6 months (induction). At 6 months, patients not experiencing a visual improvement from baseline Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity or not showing a reduction in PED height (based on optical coherence tomography [OCT]) were deemed ranibizumab nonresponders and received no further injections but underwent re-evaluation at 12 months. Patients deemed responders continued with OCT-guided active treatment on an as-needed basis for an additional 6 months.nnnRESULTSnTwenty-four patients (82.8%) were ranibizumab responders and 5 were (17.2%) nonresponders. For ranibizumab responders, mean ETDRS visual acuity improved by 7.2 ± 9.8 letters at 6 months (p = 0.002) and 6.3 ± 8.6 letters at 12 months (p = 0.002). Ranibizumab nonresponders experienced a decline in mean visual acuity of 8.2 ± 4.6 letters at 6 months (p = 0.02) and 18.2 ± 10.11 letters at 12 months (p = 0.02). At baseline, responders had a mean PED height of 345.8 ± 96.0 μm, which decreased to 111.6 ± 133.2 μm at 6 months (p < 0.001) and had a slight increase at 12 months to 144.8 ± 146.3 μm (p < 0.001). Two responders (8.3%) and 2 nonresponders (40%) developed retinal pigment epithelium tears while on treatment.nnnCONCLUSIONSnIntravitreal ranibizumab appears to be a well-tolerated treatment option for patients with fibrovascular PED. Further large-scale, prospective studies may assist in delineating the best treatment protocol.

Vision loss and vascular compromise with facial and periocular injections.

swelling, numbness, and linear whitish wheals. It is generally accepted that these adverse events are temporary and do not affect the cosmetic outcome or induce significant sequelae. However, no reports have included adverse effects to the cornea, although the procedure is performed near the eyes. It was thought that the corneal opacity in this case was caused by inaccurate targeting with IFUS and IFUS treatment that was applied close to the delicate eyelid skin. IFUS can create a focal thermal injury to the SMAS. Eyelid skin is the thinnest skin on the human body and has little connective tissue. The average thickness of eyelid skin is 521 115.8 mm in the upper eyelid of Korean individuals and varies from 0.013 to 0.014 mm in white individuals. Therefore, exact targeting of IFUS is difficult, and IFUS can injure adjacent tissue. The eyeball and eyelids are very sensitive organs, so a small injury can cause distinct discomfort. Therefore, a protective device for the eyeball, including the cornea or conjunctivae, is necessary. We hypothesized that wound contraction results from 2 mechanisms: first, collagen shrinkage due to coagulation of collagen; and second, inflammatory shrinkage occurring due to myofibroblasts. First, collagen in the corneal stroma is mostly type I, with smaller amounts of types III, V, and VI. These collagen molecules are distinguished from other extracellular matrix components by their triple-helical conformation with alpha and beta cross-links. The thermal effect of IFUS shrinks the intermolecular alpha cross-links of collagen in the cornea, and collagen shrinkage in the cornea due to IFUS results in a density change of the cornea. That effect could induce unexpected scattering or refraction of light and create corneal astigmatism. The corneal wound healing process begins after thermal damage has occurred. Second, an inflammatory response occurs due to myofibroblasts. Corneal haze is associated with activation, migration, and differentiation of stromal keratocytes to corneal myofibroblasts. Myofibroblasts have alpha smooth muscle actin, which contracts wounds, resulting in corneal haze and astigmatism. The astigmatism-induced corneal opacity improved after topical steroid application in our case, as topical steroid agents inhibit collagen synthesis, enhance collagen remodeling, and reduce corneal wound contracture. Therefore, topical steroid eye drops may relieve wound contracture due to collagen shrinkage because of collagen remodeling. Second, steroids are anti-inflammatory agents