A 5-Year Retrospective Assessment of Clinical Presentation Associated With Sports Injury in Young People Presenting to a Tertiary Eye Center.

PURPOSE: To examine the incidence and initial presentation of sports-related ocular injury in youth. METHODS: This retrospective case series study was performed at Massachusetts Eye and Ear, Boston, Massachusetts. Inclusion criteria were visit dates between January 1, 2010 and December 31, 2015, age 5 to 25 years, an ocular injury International Classifcation of Disease code, and a sports-related mechanism of injury. RESULTS: The final sample was 223 patients, representing approximately 20% of all youth eye injuries (mean age: 16.2 years (range: 6 to 24 years); 78.9% boys, 21.2% girls). The most common diagnosis was hyphema (72.2%). Most injuries occurred with soccer (23.3%), baseball (17.0%), and basketball (11.7%), with a mean visual acuity of 20/40, 20/50, and 20/50, respectively. The injuries with the lowest mean visual acuity resulted from paintball (20/500) and airsoft gun shooting (20/200). Thirty-three patients (14.7%) required surgical intervention. The average number of follow-up visits within 1 year was five. CONCLUSIONS: Approximately 20% of youth ocular injury visits were sports related, with male teenagers affected most. Hyphema was the most common type of sports-related eye injury posing a lifelong risk of ocular complications. Popular youth sports such as soccer, baseball, and basketball caused the most eye injuries. Shooting sports with paintball and airsoft guns were associated with the greatest loss of vision. Patients infrequently reported the use of protective eyewear at the time of injury. Protective eye equipment should be worn by youth participating in sports to prevent ocular trauma and the potential for surgical intervention. [J Pediatr Ophthalmol Strabismus. 2021;58(6):377-384.].

The Use of Mobile Applications as Low-Vision Aids: A Pilot Study.

OBJECTIVE: To determine the most commonly used and highest-rated mobile applications (apps) for low-vision aids. METHODS: This was a convenience sample survey. Patients known to use low-vision apps at a nonprofit low-vision center (INSIGHT, Warwick, RI) were contacted by phone between June and September 2019. INCLUSION CRITERIA: age 18+, Snellen visual acuity (VA) below 20/70, and the use of low-vision mobile apps for at least one month. A standardized script was used to record survey data and app ratings were evaluated by patients with a scale of one to five, one being the lowest and five being the highest. RESULTS: Of the sample (n=11), nine patients (81.8%) stated they used an iPhone for low-vision mobile apps. A list of 14 mobile apps was identified: the two most commonly used apps were Seeing AI (81.8%) and Be My Eyes (63.6%); their average ratings were 4.43/5 and 4.75/5, respectively. CONCLUSIONS: This survey suggests that Seeing AI and Be My Eyes are useful apps to help low- vision patients with activities of daily living.

Treatment regimens for administration of anti-vascular endothelial growth factor agents for neovascular age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is one of the leading causes of permanent blindness worldwide. The current mainstay of treatment for neovascular AMD (nAMD) is intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents: aflibercept, ranibizumab, and off-label bevacizumab. Injections can be given monthly, every two or three months ('extended-fixed'), or as needed (pro re nata (PRN)). A variant of PRN is 'treat-and-extend' whereby injections are resumed if recurrence is detected and then delivered with increasing intervals. Currently, injection frequency varies among practitioners, which underscores the need to characterize an optimized approach to nAMD management. OBJECTIVES: To investigate the effects of monthly versus non-monthly intravitreous injection of an anti-VEGF agent in people with newly diagnosed nAMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, and three trials registers from 2004 to October 2019; checked references; handsearched conference abstracts; and contacted pharmaceutical companies to identify additional studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared different treatment regimens for anti-VEGF agents in people with newly diagnosed nAMD. We considered standard doses only (ranibizumab 0.5 mg, bevacizumab 1.25 mg, aflibercept 2.0 mg, or a combination of these). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for trial selection, data extraction, and analysis. MAIN RESULTS: We included 15 RCTs. The total number of participants was 7732, ranging from 37 to 2457 in each trial. The trials were conducted worldwide. Of these, six trials exclusively took place in the US, and three included centers from more than one country. Eight trials were at high risk of bias for at least one domain and all trials had at least one domain at unclear risk of bias. Seven trials (3525 participants) compared a PRN regimen with a monthly injection regimen, of which five trials delivered four to eight injections using standard PRN and three delivered nine or 10 injections using a treat-and-extend regimen in the first year. The overall mean change in best-corrected visual acuity (BCVA) at one year was +8.8 letters in the monthly injection group. Compared to the monthly injection, there was moderate-certainty evidence that the mean difference (MD) in BCVA change at one year for the standard PRN subgroup was -1.7 letters (95% confidence interval (CI) -2.8 to -0.6; 4 trials, 2299 participants), favoring monthly injections. There was low-certainty evidence of a similar BCVA change with the treat-and-extend subgroup (0.5 letters, 95% CI -3.1 to 4.2; 3 trials, 1226 participants). Compared to monthly injection, there was low-certainty evidence that fewer participants gained 15 or more lines of vision with standard PRN treatment at one year (risk ratio (RR) 0.87, 95% CI 0.76 to 0.99; 4 trials, 2299 participants) and low-certainty evidence of a similar gain with treat-and-extend versus monthly regimens (RR 1.11, 95% CI 0.91 to 1.36; 3 trials, 1169 participants). The mean change in central retinal thickness was a decrease of -166 µm in the monthly injection group; the MD compared with standard PRN was 21 µm (95% CI 6 to 32; 4 trials, 2215 participants; moderate-certainty evidence) and with treat-and extend was 22 µm (95% CI 37 to -81 µm; 2 trials, 635 participants; low-certainty evidence), in favor of monthly injection. Only one trial (498 participants) measured quality of life and reported no evidence of a difference between regimens, but data could not be extracted (low-certainty evidence). Both PRN regimens (standard and 'treat-and-extend') used fewer injections than monthly regimens (standard PRN: MD -4.6 injections, 95% CI -5.4 to -3.8; 4 trials, 2336 participants; treat-and-extend: -2.4 injections, 95% CI -2.7 to -2.1 injections; moderate-certainty evidence for both comparisons). Two trials provided cost data (1105 participants, trials conducted in the US and the UK). They found that cost differences between regimens were reduced if bevacizumab rather than aflibercept or ranibizumab were used, since bevacizumab was less costly (low-certainty evidence). PRN regimens were associated with a reduced risk of endophthalmitis compared with monthly injections (Peto odds ratio (OR) 0.13, 95% CI 0.04 to 0.46; 6 RCTs, 3175 participants; moderate-certainty evidence). Using data from all trials included in this review, we estimated the risk of endophthalmitis with monthly injections to be 8 in every 1000 people per year. The corresponding risk for people receiving PRN regimens was 1 in every 1000 people per year (95% CI 0 to 4). Three trials (1439 participants) compared an extended-fixed regimen (number of injections reported in only one large trial: 7.5 in one year) with monthly injections. There was moderate-certainty evidence that BCVA at one year was similar for extended-fixed and monthly injections (MD in BCVA change compared to extended-fixed group: -1.3 letters, 95% CI -3.9 to 1.3; RR of gaining 15 letters or more: 0.94, 95% CI 0.80 to 1.10). The change in central retinal thickness was a decrease of 137 µm in the monthly group; the MD with the extended-fixed group was 8 µm (95% CI -11 to 27; low-certainty evidence). The frequency of endophthalmitis was lower in the extended-fixed regimen compared to the monthly group, but this estimate was imprecise (RR 0.19, 95% CI 0.03 to 1.11; low-certainty evidence). If we assumed a risk of 8 cases of endophthalmitis in 1000 people receiving monthly injections over one year, then the corresponding risk with extended-fixed regimen was 2 in 1000 people (95% CI 0 to 9). Other evidence comparing different extended-fixed or PRN regimens yielded inconclusive results. AUTHORS' CONCLUSIONS: We found that, at one year, monthly regimens are probably more effective than PRN regimens using seven or eight injections in the first year, but the difference is small and clinically insignificant. Endophthalmitis is probably more common with monthly injections and differences in costs between regimens are higher if aflibercept or ranibizumab are used compared to bevacizumab. This evidence only applies to settings in which regimens are implemented as described in the trials, whereas undertreatment is likely to be common in real-world settings. There are no data from RCTs on long-term effects of different treatment regimens.

The Ocular Manifestations and Transmission of COVID-19: Recommendations for Prevention.

BACKGROUND: Coronavirus disease-2019 (COVID-19), caused by a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been linked to ocular signs and symptoms in several case reports. Research has demonstrated that SARS-CoV-2 is spread primarily through close contact via respiratory droplets, but there is the possibility for ocular transmission, with the conjunctiva as a conduit as well as a source of infection. DISCUSSION: Ocular manifestations of SARS-CoV-2 include follicular conjunctivitis, and have been repeatedly noted as an initial or subsequent symptom of COVID-19-positive patients. Particularly in patients with ocular manifestations, there is evidence that the virus may present in tears, based on the detection of SARS-CoV-2 in conjunctival swab samples via reverse transcription polymerase chain reaction. The virus may therefore be transmittable from the ocular surface to a new host via contact with the ocular mucosa, tears, or subsequent fomites. CONCLUSIONS: All health care professionals should ask patients about ocular symptoms consistent with SARS-CoV-2, and use eye protection such as goggles or face shields as part of the standard personal protective equipment for high-risk patients in addition to wearing of masks by both the patient and provider, and should consider tears to be potentially infectious.

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to AMD accounts for most cases of AMD-related severe vision loss. Intravitreous injection of anti-vascular endothelial growth factor (anti-VEGF) agents aims to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, to improve vision. OBJECTIVES: • To investigate ocular and systemic effects of, and quality of life associated with, intravitreous injection of three anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) versus no anti-VEGF treatment for patients with neovascular AMD• To compare the relative effects of one of these anti-VEGF agents versus another when administered in comparable dosages and regimens SEARCH METHODS: To identify eligible studies for this review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (searched January 31, 2018); MEDLINE Ovid (1946 to January 31, 2018); Embase Ovid (1947 to January 31, 2018); the Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to January 31, 2018); the International Standard Randomized Controlled Trials Number (ISRCTN) Registry (www.isrctn.com/editAdvancedSearch - searched January 31, 2018); ClinicalTrials.gov (www.clinicaltrials.gov - searched November 28, 2018); and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en - searched January 31, 2018). We did not impose any date or language restrictions in electronic searches for trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or versus a control treatment (e.g. sham treatment, photodynamic therapy), in which participants were followed for at least one year. DATA COLLECTION AND ANALYSIS: Two review authors independently screened records, extracted data, and assessed risks of bias. We contacted trial authors for additional data. We compared outcomes using risk ratios (RRs) or mean differences (MDs). We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 16 RCTs that had enrolled a total of 6347 participants with neovascular AMD (the number of participants per trial ranged from 23 to 1208) and identified one potentially relevant ongoing trial. Six trials compared anti-VEGF treatment (pegaptanib, ranibizumab, or bevacizumab) versus control, and 10 trials compared bevacizumab versus ranibizumab. Pharmaceutical companies conducted or sponsored four trials but funded none of the studies that evaluated bevacizumab. Researchers conducted these trials at various centers across five continents (North and South America, Europe, Asia, and Australia). The overall certainty of the evidence was moderate to high, and most trials had an overall low risk of bias. All but one trial had been registered prospectively.When compared with those who received control treatment, more participants who received intravitreous injection of any of the three anti-VEGF agents had gained 15 letters or more of visual acuity (risk ratio [RR] 4.19, 95% confidence interval [CI] 2.32 to 7.55; moderate-certainty evidence), had lost fewer than 15 letters of visual acuity (RR 1.40, 95% CI 1.27 to 1.55; high-certainty evidence), and showed mean improvement in visual acuity (mean difference 6.7 letters, 95% CI 4.4 to 9.0 in one pegaptanib trial; mean difference 17.8 letters, 95% CI 16.0 to 19.7 in three ranibizumab trials; moderate-certainty evidence) after one year of follow-up. Participants treated with anti-VEGF agents showed improvement in morphologic outcomes (e.g. size of CNV, central retinal thickness) compared with participants not treated with anti-VEGF agents (moderate-certainty evidence). No trial directly compared pegaptanib versus another anti-VEGF agent and followed participants for one year; however, when compared with control treatments, ranibizumab and bevacizumab each yielded larger improvements in visual acuity outcomes than pegaptanib.Visual acuity outcomes after bevacizumab and ranibizumab were similar when the same RCTs compared the same regimens with respect to gain of 15 or more letters of visual acuity (RR 0.95, 95% CI 0.81 to 1.12; high-certainty evidence) and loss of fewer than 15 letters of visual acuity (RR 1.00, 95% CI 0.98 to 1.02; high-certainty evidence); results showed similar mean improvement in visual acuity (mean difference [MD] -0.5 letters, 95% CI -1.5 to 0.5; high-certainty evidence) after one year of follow-up, despite the substantially lower cost of bevacizumab compared with ranibizumab. Reduction in central retinal thickness was less among bevacizumab-treated participants than among ranibizumab-treated participants after one year (MD -11.6 µm, 95% CI -21.6 to -1.7; high-certainty evidence); however, this difference is within the range of measurement error, and we did not interpret it to be clinically meaningful.Ocular inflammation and increased intraocular pressure (IOP) after intravitreal injection were the most frequently reported serious ocular adverse events. Researchers reported endophthalmitis in less than 1% of anti-VEGF-treated participants and in no cases among control groups. The occurrence of serious systemic adverse events was comparable across anti-VEGF-treated groups and control groups; however, the numbers of events and trial participants may have been insufficient to show a meaningful difference between groups (evidence of low- to moderate-certainty). Investigators rarely measured and reported data on visual function, quality of life, or economic outcomes. AUTHORS' CONCLUSIONS: Results of this review show the effectiveness of anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) in terms of maintaining visual acuity; studies show that ranibizumab and bevacizumab improved visual acuity in some eyes that received these agents and were equally effective. Available information on the adverse effects of each medication does not suggest a higher incidence of potentially vision-threatening complications with intravitreous injection of anti-VEGF agents compared with control interventions; however, clinical trial sample sizes were not sufficient to estimate differences in rare safety outcomes. Future Cochrane Reviews should incorporate research evaluating variable dosing regimens of anti-VEGF agents, effects of long-term use, use of combination therapies (e.g. anti-VEGF treatment plus photodynamic therapy), and other methods of delivering these agents.

Cost and Selection of Ophthalmic Anti-Vascular Endothelial Growth Factor Agents.

Anti-vascular endothelial growth factor (anti-VEGF) drugs - ranibizumab, aflibercept, and off-label bevacizumab - are vital to the treatment of common retinal diseases, including exudative age-related macular degeneration (AMD), diabetic macular edema (DME), and macular edema (ME) associated with retinal vein occlusion (RVO). Given the high prevalence of AMD and retinal vascular diseases, anti-VEGF agents represent a large cost burden to the United States (US) healthcare system. Although ranibizumab and aflibercept are 30-fold more expensive per injection than bevacizumab, the two more costly medications are commonly used in the US, even though all three have been shown to be effective and safe for treatment of these retinal diseases. We investigated the availability and content of professional ophthalmic guidelines on cost consideration in the selection of anti-VEGF agents. We found that current professional guidelines were limited in availability and lacked specific guidance on cost-based anti-VEGF drug selection. This represents a missed opportunity to encourage the practice of value-based medicine. [Full article available at http://rimed.org/rimedicaljournal-2016-05.asp, free with no login].

Intravitreal Bevacizumab Versus Ranibizumab for Treatment of Neovascular Age-Related Macular Degeneration: Findings from a Cochrane Systematic Review.

TOPIC: To summarize the relative effects of bevacizumab (Avastin; Genentech, Inc, South San Francisco, CA) and ranibizumab (Lucentis; Genentech, Inc.), using findings from a Cochrane Eyes and Vision Group systematic review. CLINICAL RELEVANCE: Neovascular age-related macular degeneration (NVAMD) is the most common cause of uncorrectable vision loss among the elderly in developed countries. Bevacizumab and ranibizumab are the most frequently used anti-vascular endothelial growth factor (VEGF) agents injected intravitreally to treat NVAMD. METHODS: For this systematic review, we included only randomized controlled trials in which the 2 anti-VEGF agents had been compared directly. The primary outcome was 1-year gain in best-corrected visual acuity (BCVA) of ≥15 letters. We followed Cochrane methods for trial selection, data extraction, and data analyses. Relative effects of bevacizumab versus ranibizumab are presented as estimated risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: We identified 6 eligible randomized controlled trials with 2809 participants. The proportion of eyes that gained ≥15 letters of BCVA by 1 year was similar for the 2 agents when the same regimens were compared (RR, 0.90; 95% CI, 0.73-1.11). The mean change in BCVA from baseline also was similar (MD, -0.5 letter; 95% CI, -1.6 to +0.6). Other BCVA and quality of life outcomes were similar for the 2 agents. One-year treatment cost with ranibizumab was 5.1 and 25.5 times the cost for bevacizumab in the 2 largest trials. Ocular adverse events were uncommon (<1%), and rates were similar for the 2 agents. CONCLUSIONS: We found no important difference in effectiveness or safety between bevacizumab and ranibizumab for NVAMD treatment, but there was a large cost difference.

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to neovascular AMD accounts for most AMD-related severe vision loss. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, aim to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, improve vision. OBJECTIVES: To investigate: (1) the ocular and systemic effects of, and quality of life associated with, intravitreally injected anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) for the treatment of neovascular AMD compared with no anti-VEGF treatment; and (2) the relative effects of one anti-VEGF agent compared with another when administered in comparable dosages and regimens. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2014), EMBASE (January 1980 to March 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 March 2014. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or a control treatment (e.g., sham treatment or photodynamic therapy). All trials followed participants for at least one year. DATA COLLECTION AND ANALYSIS: Two review authors independently screened records, extracted data, and assessed risks of bias. We contacted trial authors for additional data. We analyzed outcomes as risk ratios (RRs) or mean differences (MDs). We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included 12 RCTs including a total of 5496 participants with neovascular AMD (the number of participants per trial ranged from 28 to 1208). One trial compared pegaptanib, three trials ranibizumab, and two trials bevacizumab versus controls; six trials compared bevacizumab with ranibizumab. Four trials were conducted by pharmaceutical companies; none of the eight studies which evaluated bevacizumab were funded by pharmaceutical companies. The trials were conducted at various centers across five continents (North and South America, Europe, Asia and Australia). The overall quality of the evidence was very good, with most trials having an overall low risk of bias.When compared with control treatments, participants who received any of the three anti-VEGF agents were more likely to have gained 15 letters or more of visual acuity, lost fewer than 15 letters of visual acuity, and had vision 20/200 or better after one year of follow up. Visual acuity outcomes after bevacizumab and ranibizumab were similar when the same regimens were compared in the same RCTs, despite the substantially lower cost for bevacizumab compared with ranibizumab. No trial directly compared pegaptanib with other anti-VEGF agents; however, when compared with controls, ranibizumab or bevacizumab yielded larger improvements in visual acuity outcomes than pegaptanib.Participants treated with anti-VEGFs showed improvements in morphologic outcomes (e.g., size of CNV or central retinal thickness) compared with participants not treated with anti-VEGF agents. There was less reduction in central retinal thickness among bevacizumab-treated participants than among ranibizumab-treated participants after one year (MD -13.97 µm; 95% confidence interval (CI) -26.52 to -1.41); however, this difference is within the range of measurement error and we did not interpret it as being clinically meaningful.Ocular inflammation and increased intraocular pressure after intravitreal injection were the most frequently reported serious ocular adverse events. Endophthalmitis was reported in fewer than 1% of anti-VEGF treated participants; no cases were reported in control groups. The occurrence of serious systemic adverse events was comparable across anti-VEGF-treated groups and control groups; however, the numbers of events and trial participants may have been insufficient to detect a meaningful difference between groups. Data for visual function, quality of life, and economic outcomes were sparsely measured and reported. AUTHORS' CONCLUSIONS: The results of this review indicate the effectiveness of anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) in terms of maintaining visual acuity; ranibizumab and bevacizumab were also shown to improve visual acuity. The information available on the adverse effects of each medication do not suggest a higher incidence of potentially vision-threatening complications with intravitreal injection compared with control interventions; however, clinical trial sample sizes may not have been sufficient to detect rare safety outcomes. Research evaluating variable dosing regimens with anti-VEGF agents, effects of long-term use, combination therapies (e.g., anti-VEGF treatment plus photodynamic therapy), and other methods of delivering the agents should be incorporated into future Cochrane reviews.

Reproducibility of macular thickness and volume using Zeiss optical coherence tomography in patients with diabetic macular edema.

PURPOSE: To evaluate optical coherence tomography (OCT) reproducibility in patients with diabetic macular edema (DME). DESIGN: Prospective 1-day observational study. PARTICIPANTS: Two hundred twelve eyes of 107 patients with DME involving the macular center by clinical examination and OCT central subfield thickness of > or =225 microm. METHODS: Retinal thickness was measured with the OCT3 system, and scans were evaluated by a reading center. Reproducibility of retinal thickness measurements was assessed, and 95% confidence intervals (CIs) for a change in thickness were estimated. MAIN OUTCOME MEASURES: Reproducibility of OCT-measured central subfield thickness. RESULTS: Reproducibility was better for central subfield thickness than for center point thickness (half-width of the 95% CI for absolute change, 38 microm vs. 50 microm, and for relative change, 11% vs. 17%, respectively; P<0.001). The median absolute difference between replicate measurements of the central subfield was 7 microm (2%). Half-widths of the 95% CI for a change in central subfield thickness were 22, 23, 33, and 56 microm for scans with central subfield thicknesses of <200, 200 to <250, 250 to <400, and > or =400 microm, respectively. When expressed as percentage differences between 2 measurements, half-widths of the 95% CI for a change in central subfield thickness were 10%, 10%, 10%, and 13% for scans with central subfield thicknesses of <200, 200 to <250, 250 to <400, and > or =400 microm, respectively. We were unable to identify an effect on reproducibility of central subfield measurements with respect to the presence of cystoid abnormalities, subretinal fluid, vitreomacular traction, or reduced visual acuity. Reproducibility was better when both scans had a standard deviation (SD) of the center point of <10.0% (half-width of the 95% CI for change, 33 microm vs. 56 microm; P<0.001). CONCLUSIONS: Reproducibility is better for central subfield thickness measurements than for center point measurements, and variability is less with retinal thickness when expressed as a percent change than when expressed as an absolute change. A change in central subfield thickness exceeding 11% is likely to be real. Scans with an SD of the center point of > or =10.0% are less reproducible and should be viewed with caution when assessing the validity of an observed change in retinal thickness in patients with DME.

Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment.

OBJECTIVE: To evaluate the safety and efficacy of intravitreal injections of an antigen-binding fragment of a recombinant humanized monoclonal antibody directed toward vascular endothelial growth factor (rhuFab VEGF) in a monkey model of choroidal neovascularization (CNV). METHODS: In phase 1 of the study, each animal received intravitreal injections, 500 microg per eye, of rhuFab VEGF in one eye (prevention eye), while the contralateral eye received rhuFab VEGF vehicle (control eye) at 2-week intervals. On day 21, laser photocoagulation was performed to induce CNV. In phase 2, the vehicle-treated eye was crossed over and both eyes received 500 microg of rhuFab VEGF beginning 21 days following laser-induced injury at days 42 and 56. The eyes were monitored by ophthalmic examinations, color photographs, and fluorescein angiography. RESULTS: rhuFab VEGF did not cause any ocular hemorrhages. All eyes treated with rhuFab VEGF developed acute anterior chamber inflammation within 24 hours of the first injection that resolved within 1 week, and this inflammation was less severe with subsequent injections. The incidence of CNV, defined angiographically, was significantly lower in the prevention eyes than the control eyes (P<.001). Subsequent treatments were associated with less leakage in eyes with established CNV that were crossed over from the control eyes to the treatment eyes (P =.001). CONCLUSIONS: Intravitreal rhuFab VEGF injections prevented formation of clinically significant CNV in cynomolgus monkeys and decreased leakage of already formed CNV with no significant toxic effects. CLINICAL RELEVANCE: This study provides the nonclinical proof of principle for ongoing clinical studies of intravitreally injected rhuFab VEGF in patients with neovascular age-related macular degeneration.