RELATIVE QUIESCENCE OF EXUDATIVE AGE-RELATED MACULAR DEGENERATION AFTER RESOLUTION OF POSTINJECTION ENDOPHTHALMITIS.

PURPOSE: To evaluate alterations in treatment burden and course of exudative age-related macular degeneration in patients who contracted endophthalmitis from intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. METHODS: Retrospective study at the University of Pittsburgh Medical Center examining frequency of anti-VEGF injections, activity of choroidal neovascularization, and visual acuity before and after endophthalmitis treatment. RESULTS: Twenty-one patients meeting inclusion criteria were identified, of whom 7 (33%) patients did not restart anti-VEGF treatment 12 months after endophthalmitis because of quiescence of exudative age-related macular degeneration without significant visual acuity loss (P > 0.05). Patients who resumed anti-VEGF treatment exhibited 32% and 38% decreases in injection frequency by 12 and 24 months after endophthalmitis, respectively (P < 0.05). On first optical coherence tomography follow-up, 10 patients exhibited quiescence of choroidal neovascularization activity, although there were no measurable changes in macular thickness (P > 0.05). No differences in post-endophthalmitis exudative age-related macular degeneration progression or treatment burden were observed when factoring adjuvant intravitreal steroid therapy, culture results, nor choroidal neovascularization subtypes. CONCLUSION: Endophthalmitis resolution is associated with a decrease in choroidal neovascularization activity and a reduction of anti-VEGF treatment burden in patients with exudative age-related macular degeneration.

Peripheral Retinal Changes Associated with Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report Number 12 by the Age-Related Eye Disease Study 2 Optos PEripheral RetinA (OPERA) Study Research Group.

PURPOSE: To compare rates of peripheral retinal changes in Age-Related Eye Disease Study 2 (AREDS2) participants with at least intermediate age-related macular degeneration (AMD) with control subjects without intermediate age-related changes (large drusen). DESIGN: Cross-sectional evaluation of clinic-based patients enrolled in AREDS2 and a prospective study. PARTICIPANTS: Participants from prospective studies. METHODS: The 200° pseudocolor and fundus autofluorescence (FAF) images were captured on the Optos 200 Tx Ultrawide-field device (Optos, Dunfermline, Scotland) by centering on the fovea and then steering superiorly and inferiorly. The montaged images were graded at a reading center with the images divided into 3 zones (zone 1 [posterior pole], zone 2 [midperiphery], and zone 3 [far periphery]) to document the presence of peripheral lesions. MAIN OUTCOME MEASURES: Peripheral retinal lesions: drusen, hypopigmentary/hyperpigmentary changes, reticular pseudodrusen, senile reticular pigmentary changes, cobblestone degeneration, and FAF abnormalities. RESULTS: A total of 484 (951 eyes) AREDS2 participants with AMD (cases) and 89 (163 eyes) controls without AMD had gradable color and FAF images. In zones 2 and 3, neovascularization and geographic atrophy (GA) were present, ranging from 0.4% to 6% in eyes of cases, respectively, and GA was present in 1% of eyes of controls. Drusen were detected in 97%, 78%, and 64% of eyes of cases and 48%, 21%, and 9% of eyes of controls in zones 2 and 3 superior and 3 inferior, respectively (P < 0.001 for all). Peripheral reticular pseudodrusen were seen in 15%. Senile reticular pigmentary change was the predominant peripheral change seen in 48% of cases and 16% of controls in zone 2 (P < 0.001). Nonreticular pigment changes were less frequent in the periphery than in the posterior pole (46% vs. 76%) and negligible in controls. CONCLUSIONS: Peripheral retinal changes are more prevalent in eyes with AMD than in control eyes. Drusen are seen in a majority of eyes with AMD in both the mid and far periphery, whereas pigment changes and features of advanced AMD are less frequent. Age-related macular degeneration may be more than a "macular" condition but one that involves the entire retina. Future longitudinal studies of peripheral changes in AMD and their impact on visual function may contribute to understanding AMD pathogenesis.

Characterization of pneumatic retinopexy failures and the pneumatic pump: a new complication of pneumatic retinopexy.

BACKGROUND: We review a three-year series of cases with pneumatic retinopexy (PR), specifically evaluating failures and suggesting a new mechanism of failure. METHODS: One hundred and thirty-five consecutive patients who underwent PR for rhegmatogenous retinal detachments were included. The primary outcome measure was the characteristics of PR failures. Secondary outcome measures included preoperative clinical characteristics. RESULTS: Seventy-five percent of the patients had successful results with PR; 100% were ultimately reattached with additional surgery. All but 1 failure (97%) occurred within the first postoperative month and 85% occurred by postoperative Day 10. The most common cause of failure was a new detachment from a new break (23 of 35 failures). Risk factors for failure included presenting visual acuity worse than 20/60 (odds ratio [OR] = 1.89), male gender (OR = 1.52), age >60 years (OR = 1.32), >2 breaks (OR = 1.28), pseudophakia/aphakia (OR = 1.20), and detachments after trabeculectomy (OR = 2.43). Lattice degeneration, high myopia (>-6.00 diopters), left eye, detachment after cataract surgery or yttrium aluminum garnet capsulotomy had minimal influence on outcome (all OR < 1.10). CONCLUSION: Characterization of PR failures will improve patient selection. We have named a new complication secondary to a patient performing the steamroller maneuver five times the "pneumatic pump."

An Optical Coherence Tomography-Based Measure as an Independent Estimate of Retinal Function in Retinitis Pigmentosa.

BACKGROUND: With the clinical advances in the field of gene therapy, the development of objective measures of visual function of patients with inherited retinal dystrophies (IRDs) is of utmost importance. Here, we propose one such measure. METHODS: We retrospectively analyzed data from a cohort of 194 eyes of 97 genetically diagnosed patients with retinitis pigmentosa (RP), the most common IRD, followed at the UPMC Vision Institute. The analyzed data included the reflectivity ratio (RR) of the retinal nerve fiber layer (RNFL) to that of the entire retina, visual acuity (VA) and the thickness of the retinal outer nuclear layer (ONL) and the RNFL. RESULTS: There was a strong positive correlation between the RR and VA. Both VA and the RR were negatively correlated with disease duration; VA, but not the RR, was negatively correlated with age. The RR correlated with the ONL but not with the RNFL thickness or the intraocular pressure. Age, RR, disease duration and ONL thickness were found to be independent predictors of VA by multivariate analysis. CONCLUSION: The OCT RR could serve as an independent predictor of visual acuity, and by extension of retinal function, in genetically diagnosed RP patients. Such objective measures can be of great value in patient selection for therapeutic trials.

Challenges in posterior uveitis-tips and tricks for the retina specialist.

PURPOSE: Posterior uveitis is a common chorioretinal pathology affecting all ages worldwide and is a frequent reason for referral to the retina clinic. The spectrum of etiologies for uveitis is very broad and includes infectious and auto-immune diseases. Inflammation can be confined to the eye or may be a part of systemic disease. A useful outline is therefore proposed to aid in the correct diagnosis of these challenging entities. The situation is further complicated by the fact that many neoplastic conditions resemble features of posterior uveitis; they are known as "masqueraders of uveitis". Here, we summarize different posterior uveitides that present with rare findings, along with masqueraders that can be difficult to distinguish. These conditions pose a diagnostic dilemma resulting in delay in treatment because of diagnostic uncertainty. METHODS: An extensive literature search was performed on the MEDLINE/PUBMED, EBSCO and Cochrane CENTRAL databases from January 1985 to January 2022 for original studies and reviews of predetermined diagnoses that include posterior uveitic entities, panuveitis and masquerade syndromes. RESULTS: We described conditions that can present as mimickers of posterior uveitis (i.e., immune check-points inhibitors and Vogt-Koyanagi-Harada-like uveitis; leukemia and lymphoma associated posterior uveitis), inflammatory conditions that present as mimickers of retinal diseases (i.e., Purtscher-like retinopathy as a presentation of systemic lupus erythematosus; central serous chorioretinopathy masquerading inflammatory exudative retinal detachment), and uveitic conditions with rare and diagnostically challenging etiologies (i.e., paradoxical inflammatory effects of anti-TNF-α; post vaccination uveitis; ocular inflammation after intravitreal injection of antiangiogenic drugs). CONCLUSION: This review of unique posterior uveitis cases highlights the overlapping features of posterior uveitis (paradoxical inflammatory effects of anti -TNF α and uveitis; Purtscher-like retinopathy as a presentation of systemic lupus erythematosus, …) and the nature of retinal conditions (ischemic ocular syndrome, or central retinal vein occlusion, amyloidosis, inherited conditions like retinitis pigmentosa, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), etc.…) that may mimic them is represented. Careful review of past uveitis history, current medications and recent vaccinations, detailed examination of signs of past or present inflammation, eventually genetic testing and/ or multimodal retinal imaging (like fluorescein angiography, EDI-OCT, OCT-angiography for lupus Purtscher-like retinopathy evaluation, or ICG for central serous retinopathy, or retinal amyloid angiopathy) may aid in correct diagnosis.

Risk factors for conversion to neovascular age-related macular degeneration based on longitudinal morphologic and visual acuity data.

PURPOSE: To use longitudinal quantitative morphologic and visual acuity (VA) data to investigate the risk of choroidal neovascularization (CNV) event occurrence in eyes with dry age-related macular degeneration (AMD). DESIGN: Prospective observational study. PARTICIPANTS: A total of 513 participants (844 eyes) followed longitudinally in one center enrolled in the Age-Related Eye Disease Study (AREDS) or the Prophylactic Treatment of AMD Study (PTAMD). METHODS: We assessed images of previously obtained fundus photographs for the presence of macular pigmentation, drusen area, and drusen distribution (number and size), and fellow eye CNV status at baseline. Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity at each visit and the age of each subject were obtained. We used a longitudinal logistic mixed-effects model with random intercepts fitted to event occurrences to assess risk on a per eye basis. MAIN OUTCOME MEASURES: Odds ratios for CNV event. RESULTS: Thirty-one subjects (6.0%) had events. Only VA changes over time and follow-up interval showed statistically significant effects. Several statistical models that included VA at the previous visit were used. In 2 models, 3 categories of VA were used: ≤ 75 letters, >75 and ≤ 85 letters, and >85 letters. Two categories were used for follow-up: ≤ 3 years versus >3 years or ≤ 1 year versus >1 year. In the first model with categorization at 3 years, a decrease in acuity from the >85 letter category to ≤ 75 letters increased the odds of CNV by 16.9 times (P = 0.022). In the model with categorization at 1 year, a decrease in acuity from the >85-letter category to ≤ 75 letters increased the odds of CNV by 21.4 times (P = 0.0175). Differences between the follow-up intervals were significant (P = 0.043) and indicated a more than 7-fold increase in the odds. Changes in morphologic features of the macula did not show significant effects. CONCLUSIONS: A decrease in VA to ≤ 75 ETDRS letters in an eye with an initial ETDRS baseline acuity of >85 letters increases the likelihood of CNV by approximately 20-fold. This likelihood also increases with aging.

Lidocaine Gel Interferes With the Antibacterial Activity of Povidone-Iodine.

BACKGROUND AND OBJECTIVE: Retina specialists use lidocaine gel as a topical anesthetic. We determined the antibacterial interaction between povidone-iodine (PI) and lidocaine gel using corneoscleral tissue as a solid phase medium. MATERIALS AND METHODS: Five pieces of corneoscleral tissue in five trials were inoculated with 1.000 colony-forming units of bacteria isolated from endophthalmitis. Inoculated corneal tissue were overlaid with nothing (control), lidocaine gel, 5% PI, lidocaine gel over 5% PI, and 5% PI over lidocaine gel for 5 minutes prior to placement in growth liquid medium at 37°C. Growth was monitored for 48 hours. RESULTS: Application of lidocaine gel prior to 5% PI application provided for the growth of the five bacterial isolates, whereas 5% PI prior to lidocaine gel prevented growth. CONCLUSION: Using corneoscleral tissue, PI and lidocaine gel appear to have an antagonistic interaction when lidocaine gel is applied initially prior to 5% PI, preventing bactericidal activity of PI. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:S13-S16.].

Comparison of StratusOCT and Cirrus HD-OCT imaging in macular diseases.

BACKGROUND AND OBJECTIVE: The Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) device is a spectral-domain optical coherence tomography system that allows faster data acquisition than the previous generation StratusOCT (Carl Zeiss Meditec, Dublin, CA), which is a time-domain device. The authors compared images from both units to determine the clinical usefulness of spectral-domain optical coherence tomography technology in patients with macular diseases. PATIENTS AND METHODS: Six consecutive patients were imaged with both the Cirrus HD-OCT and the StratusOCT devices and the images were compared. RESULTS: Cirrus HD-OCT images were typically more useful than StratusOCT images for assessing fine architectural details in macular pathology. The Cirrus HD-OCT software also facilitated a better understanding of three-dimensional data volumes. CONCLUSIONS: Commercially available spectral-domain optical coherence tomography is a clinically useful tool for visualizing and understanding macular diseases and offers benefits not inherent in previous generation machines.

Prophylactic treatment of age-related macular degeneration report number 2: 810-nanometer laser to eyes with drusen: bilaterally eligible patients.

BACKGROUND AND OBJECTIVE: To determine the prophylactic and therapeutic value of a single subthreshold 810-nanometer laser treatment in patients with high risk drusen as a manifestation of dry age-related macular degeneration in both eyes. PATIENTS AND METHODS: The Prophylactic Treatment of Age-related Macular Degeneration study enrolled 1,278 eyes of 639 participants who were 50 years or older with at least 5 drusen 63 microm or more in diameter in each eye. Treatment consisted of the placement of an annular grid of 48 extrafoveal, subthreshold 810-nm diode laser applications centered at but sparing the foveola in one eye of each participant, with the fellow eye serving as a control. Development of choroidal neovascularization and change in best-corrected visual acuity were compared between treated and untreated eyes. RESULTS: Subthreshold laser treatment did not decrease the incidence of choroidal neovascularization in treated versus untreated eyes. A modest visual acuity benefit in treated eyes was found at 24 months (1.5 letter difference; P = .04) and in the treated eyes of participants with a baseline visual acuity between 20/32 and 20/63 (4.0 letter difference; P = .0034). However, this treatment effect was not sustained at 3 years. CONCLUSION: A single subthreshold 810-nanometer laser treatment to eyes of participants with bilateral high risk drusen is not an effective prophylactic strategy against choroidal neovascularization.

Biomechanical assessment of radial optic neurotomy.

PURPOSE: A biomechanical model was constructed to simulate the potential therapeutic effect that the surgical procedure radial optic neurotomy (RON) would have on an eye with a central retinal vein occlusion. DESIGN: Experimental study. CONTROLS: Model eyes undergoing RON were compared to control eyes under the same baseline conditions. INTERVENTION: Radial optic neurotomy. We modeled the optic nerve, lamina cribrosa, and the sclera separately and then reassembled the components. Material properties of the sclera and lamina cribrosa were extracted from the literature and both stiff and more elastic values were used for the optic nerve. Intraocular and arterial pressures were varied across a wide range in the analysis. MAIN OUTCOME MEASURE: Change in central retinal vein lumen size. RESULTS: Over a clinically relevant range of boundary conditions, the increase in the lumen area of the central retinal vein lumen after RON remained trivial, ranging from 1% to a maximum of 5%. CONCLUSIONS: The biomechanical effect of RON is negligible, and is unlikely to be a procedure that could mechanically ameliorate the clinical sequelae of a central vein occlusion.

Diminished perception of light as a symptom of depression: further studies.

BACKGROUND: In a previous preliminary report, the perception of a decrease in ambient light intensity appeared to be correlated with depression. We prospectively studied this potential link in a controlled study. METHODS: The question, "I've noticed that the lights in my surroundings seem dimmer than usual", was added to the Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire and administered prospectively to 213 subjects 50-80 years of age participating in the Age-Related Eye Disease Study (AREDS). All had visual acuity of 20/32 or better in at least one eye. Main outcome measures were the relationship between the dimness question answer and severity of depression, and the likelihood that patients reporting dimness were depressed. RESULTS: Subjects endorsing their surroundings as being dimmer than usual at least some of the time had a mean CES-D score of 10.6 (SD=7.0) compared to a mean of 5.5 (SD=5.4) for subjects who never noted dimness (t=-4.22, p=.0001). Depressed individuals (CES-D > or = 16) were significantly more likely to report dimness than non-depressed (CES-D<16) subjects (chi(2)=15.6, p<0.0001). The total CES-D score and the degree of reported dimness (0-3) were significantly associated (r=0.31, p<.0001). Using a stepwise regression analysis, subjects who reported any dimness were more likely to be depressed. LIMITATIONS: A relatively small number of subjects, 38 (18%), reported dimness requiring us to dichotomize their dimness level in some analyses. CONCLUSIONS: Perceived dimness of one's ambient surroundings and clinical depression are linked. Health care professionals should inquire about this symptom in potentially depressed patients.

Vitreous substitute removal rates with the Accurus and Millennium vitrectomy systems.

Recent innovations in vitrectors have led to studies of evaluated aspiration rates of basic saline solution, porcine vitreous, and human vitreous, but each of these substances has potential drawbacks. The authors determined the timed removal rates of egg white with the Accurus 20-, 23-, and 25-gauge vitreous cutters (Alcon Laboratories, Inc., Fort Worth, TX) and the Millennium AVE 20- and 25-gauge system (Bausch & Lomb, St. Louis, MO and MID Labs, Inc., San Diego, CA) using various machine parameters. The Accurus 20- and 23-gauge cutters and the Millennium AVE 20- and 25-gauge cutters removed egg white easily. At higher cut rates, where slow and delicate removal of vitreous is typically desired, the probes, as expected, removed egg white more slowly.

Ultrawide angle fluorescein angiographic imaging: a comparison to conventional digital acquisition systems.

BACKGROUND AND OBJECTIVE: A prototype ultrawide field angiographic system and conventional technology were compared. PATIENTS AND METHODS: Thirty subjects with diabetic retinopathy were imaged in three centers by conventional (Topcon Inc., Paramus, NJ, or Carl Zeiss Meditec, Dublin, CA) and ultrawide field (Optos P200A; Optos Inc., Dunfermline, Scotland) digital fluorescein angiography units. A calibrated grid was digitally placed on the images to facilitate measurements. Main outcome measures were field of view and the number of grid sectors displaying retinal ischemia and neovascularization. Secondary measures were image quality and patient satisfaction scores. RESULTS: The P200A provided a significantly greater visual field extent of 8.7 +/- 1.6 disc diameters (DD) compared to the conventional systems (3.4 +/- 0.76 DD) (P < .001). Retinal ischemia was better revealed (16.9 +/- 15 vs 3.4 +/- 4.26 sectors) with the prototype, but image quality was superior with the conventional system. Patient satisfaction scores did not differ between systems. CONCLUSION: A prototype ultrawide angle imaging system displayed significantly more diabetic retinal pathology in a single image than conventional systems.

Morphological and Angiographic Peripheral Retinal Changes in Patients with Age-Related Macular Degeneration.

OBJECTIVE: To show morphologic and angiographic changes in the peripheral retina in patients with age-related macular degeneration (AMD) using wide-field fundus imaging, and to compare these findings with those from healthy controls. DESIGN: Cross-sectional clinical study. PARTICIPANTS: In total, 152 patients with clinical AMD and 150 healthy controls (without AMD in either macula) were studied. Subjects were ≥50 years of age. Exclusion criteria were diabetic retinopathy, previous retinal surgery, high myopia, or dense cataract, as well as any retinal inflammatory, degenerative, or occlusive disease. METHODS: For both groups of patients, color fundus images were captured with the Optos P200 MA camera (Optos, Dunfermline, Scotland). Image analysis software was used to characterize each image. Angiography was performed on the AMD group only. Morphological and angiographic peripheral retinal changes were studied per the frequency of their occurrence, the affected peripheral retina (clock hours), and the localization of peripheral changes with regard to the eye equator. Statistical significance was defined at a level of P < 0.05. MAIN OUTCOME MEASURES: Peripheral changes in both groups according to their type and frequency (percentage of eyes with detected retinal changes), the number of clock hours of affected peripheral retina, and their localization with regard to the equator of the eye. RESULTS: Drusen, reticular pigmentary changes, and paving stone degeneration occurred more frequently in the AMD group than in controls (P < 0.001, P < 0.001, and P < 0.001 respectively), whereas white without pressure occurred more frequently in the control group (P = 0.027). In both groups, peripheral retinal changes were observed peripheral to the equator in more than 40% of analyzed eyes. In control Croatian subjects, peripheral drusen were seen in 38% of subjects compared with 68% of AMD subjects. CONCLUSION: Drusen, reticular pigmentary change , and paving stone degeneration occur significantly more frequently in subjects with AMD compared with controls. White without pressure degeneration was present in a high percentage of control subjects.

Computerized detection and measurement of drusen in age-related macular degeneration.

BACKGROUND AND OBJECTIVE: The authors used a drusen detection algorithm to quantitate drusen on digitized images and determined its precision and accuracy. PATIENTS AND METHODS: Fundus images from 349 participants in the Age-Related Eye Disease Study trial were digitized and analyzed with the Drusen Analyzer (IRIDEX Corporation, Mountain View, CA). The size, number, and area of the drusen in two macular regions were computed by two readers using an interactive approach. Measurements were compared to data generated by reading center methods. RESULTS: For the Analyzer, inter-observer agreement was 0.79 (SE = 0.02) and 0.86 (SE = 0.01) (kappa statistic). Intra-observer precision was 0.835 and 0.880 (Spearman coefficients). Categorical agreement (weighted kappa) between the Analyzer and reading center results for the two regions was (0.76, 0.58) and (0.68, 0.68) for readers A and B. The time required to quantitate an image using the Analyzer was 105 +/- 52 and 218 +/- 102 seconds for the two regions, respectively. CONCLUSIONS: Quantitative detection of drusen can be performed reproducibly and efficiently. Comparisons to more labor intensive reading center techniques suggest that the results are similar but that the algorithm is more sensitive and precise.

Panretinal photocoagulation and photodynamic therapy for anterior segment neovascularization secondary to ischemic central retinal vein occlusion.

BACKGROUND AND OBJECTIVE: To compare the effects of panretinal photocoagulation (PRP) and photodynamic therapy (PDT) for anterior segment neovascularization secondary to ischemic central retinal vein occlusion (CRVO). PATIENTS AND METHODS: Fifty-seven eyes were randomized to receive standard PRP (19 eyes), selective PRP (20 eyes), or PDT (17 eyes). Selective PRP was performed only when iris neovascularization and/or angle neovascularization showed progression on weekly follow-up. Primary outcome measures were the extension of anterior segment neovascularization and the rate of neovascular glaucoma development. Secondary outcome measures included visual acuity results. RESULTS: After 12 months of follow-up, iris neovascularization extension was 0.52, 2.55, and 2.27 in the PRP, selective PRP, and PDT groups, respectively. Anterior segment neovascularization extension was 0.57, 1.50, and 1.27 in the PRP, selective PRP, and PDT groups, respectively. Both showed a statistically significant difference in the PRP group. The rate of neovascular glaucoma development was similar in the three groups. CONCLUSIONS: Although PRP was better at determining iris neovascularization and anterior segment neovascularization regression, the similar rate of neovascular glaucoma development found in the three groups indicates that anterior segment neovascularization secondary to ischemic CRVO can also be safely managed using selective PRP or PDT.

Ranibizumab-pegaptanib therapy for idiopathic choroidal neovascularization: report of a case.

Idiopathic choroidal neovascularization is a rather uncommon condition in children and young adults. While some cases resolve spontaneously, in this case visual acuity deteriorated from 20/25 to 20/80 in the affected eye of a 20-year-old college student. After weighing numerous treatment options, she was treated with an intravitreal injection of Ranibizumab (Lucentis) which induced an involution of the membrane over one month's time. Vision recovered to 20/20-1. A follow-up injection with Pegaptanib sodium (Macugen) was administered to promote further involution of the membrane. Vision remained stable over the next four months with no recurrence of the membrane.

Intravitreal ranibizumab and bevacizumab: a review of risk.

Ranibizumab (Lucentis), a recombinant monoclonal antibody, blocks all active forms of vascular endothelial growth factor A and was the first treatment for age-related macular degeneration shown to improve visual acuity in a substantial percentage of patients rather than slowing visual loss. Bevacizumab (Avastin) has a similar action, is related to the ranibizumab compound with respect to its structure, but has not been approved by the FDA for intravitreal use and therefore must be utilized only in an off-label setting. While ranibizumab was approved by the FDA at a dose of 0.5 mg per intravitreal injection, the manufacturer recently issued a letter to physicians warning of the increased risk of stroke at the FDA-approved dose as compared to a lower studied dose of 0.3 mg. An interim analysis of the ongoing SAILOR study revealed a 1.2% risk of stroke in the 0.5 mg arm versus 0.3% in the 0.3 mg arm (p = 0.02). It is unclear whether the trend toward a higher risk of stroke in patients receiving 0.5 mg dose of ranibizumab would persist in the final analysis, but details such as causality, topography, and severity of stroke in the SAILOR study should also be delineated. The risks of intraocular use of bevacizumab remain largely unknown at this time.