Comprehensive Ocular and Systemic Safety Evaluation of Polysialic Acid-Decorated Immune Modulating Therapeutic Nanoparticles (PolySia-NPs) to Support Entry into First-in-Human Clinical Trials.

An inflammation-resolving polysialic acid-decorated PLGA nanoparticle (PolySia-NP) has been developed to treat geographic atrophy/age-related macular degeneration and other conditions caused by macrophage and complement over-activation. While PolySia-NPs have demonstrated pre-clinical efficacy, this study evaluated its systemic and intraocular safety. PolySia-NPs were evaluated in vitro for mutagenic activity using Salmonella strains and E. coli, with and without metabolic activation; cytotoxicity was evaluated based on its interference with normal mitosis. PolySia-NPs were administered intravenously in CD-1 mice and Sprague Dawley rats and assessed for survival and toxicity. Intravitreal (IVT) administration in Dutch Belted rabbits and non-human primates was assessed for ocular or systemic toxicity. In vitro results indicate that PolySia-NPs did not induce mutagenicity or cytotoxicity. Intravenous administration did not show clastogenic activity, effects on survival, or toxicity. A single intravitreal (IVT) injection and two elevated repeat IVT doses of PolySia-NPs separated by 7 days in rabbits showed no signs of systemic or ocular toxicity. A single IVT inoculation of PolySia-NPs in non-human primates demonstrated no adverse clinical or ophthalmological effects. The demonstration of systemic and ocular safety of PolySia-NPs supports its advancement into human clinical trials as a promising therapeutic approach for systemic and retinal degenerative diseases caused by chronic immune activation.

Use of Corticosteroids in the Treatment of Patients With Diabetic Macular Edema Who Have a Suboptimal Response to Anti-VEGF: Recommendations of an Expert Panel.

BACKGROUND AND OBJECTIVE: Guidance on the use of corticosteroids in the treatment of diabetic macular edema (DME) is lacking. This study aimed to develop a clinically recommended treatment paradigm for DME with emphasis on the role of corticosteroids. PATIENTS AND METHODS: An expert panel of nine retinal specialists in the United States developed consensus recommendations for DME treatment through a modified Delphi process. RESULTS: The panelists typically use intravitreal injections of vascular endothelial growth factor (VEGF) antagonists as first-line treatment of DME and switch patients with an inadequate response to anti-VEGF therapy (failure of best-corrected visual acuity to improve to 20/40 or better because of edema after three to six monthly injections, or a less-than-50% reduction in excess macular thickness after three to four monthly injections) to intravitreal corticosteroid treatment. CONCLUSION: Intravitreal corticosteroids have a potentially useful role in the treatment of patients with DME who have an inadequate response to intravitreal anti-VEGF therapy. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:291-301.].

A multicenter, 12-month randomized study comparing dexamethasone intravitreal implant with ranibizumab in patients with diabetic macular edema.

PURPOSE: To evaluate whether treatment with dexamethasone intravitreal implant (DEX implant) 0.7 mg every 5 months provides a similar average change in best-corrected visual acuity (BCVA) from baseline as ranibizumab 0.5 mg administered as per its European Summary of Product Characteristics in patients with diabetic macular edema (DME). METHODS: This was a multicenter, open-label, 12-month, randomized, parallel-group, noninferiority study in patients with DME (one eye/patient). The primary efficacy measure was BCVA using the Early Treatment Diabetic Retinopathy Study (ETDRS) method. Secondary efficacy measures included area of leakage on fluorescein angiography and central retinal thickness (CRT) on optical coherence tomography. RESULTS: Baseline patient characteristics were similar in the two treatment groups (DEX implant, n = 181; ranibizumab, n = 182); mean DME duration was ∼33 months. The mean average BCVA change from baseline over 12 months was 4.34 letters with DEX implant and 7.60 letters with ranibizumab. The lower limit of the 95 % confidence interval of the between-group difference was -4.74 letters, and therefore, DEX was demonstrated to be noninferior to ranibizumab based on the prespecified noninferiority margin of 5 letters. At monthly follow-up visits, the percentage of patients with ≥15-letter BCVA gain from baseline ranged from 7.2 to 17.7 % with DEX implant and 4.4 to 26.9 % with ranibizumab. Both DEX implant and ranibizumab effectively reduced CRT and reduced the area of fluorescein leakage. Between-group differences in change from baseline CRT favored DEX implant at 1, 2, 6, and 7 months (p ≤ 0.007) and ranibizumab at 4, 5, 9, and 10 months (p < 0.001); the decrease in fluorescein leakage area was greater with DEX implant than ranibizumab at month 12 (p < 0.001). Ocular adverse events in the study eye were more frequent in the DEX implant group because of the occurrence of intraocular pressure (IOP) increases and cataract. IOP increases were transient and generally managed with topical medication. CONCLUSIONS: Both DEX implant and ranibizumab were well tolerated and improved BCVA and anatomic outcomes in patients with DME. DEX implant met the a priori criterion for noninferiority to ranibizumab in average change from baseline BCVA over 12 months. Noninferiority was achieved with an average of 2.85 DEX implant injections and 8.70 ranibizumab injections per patient.

Dexamethasone intravitreal implant in combination with laser photocoagulation for the treatment of diffuse diabetic macular edema.

PURPOSE: To evaluate Ozurdex (dexamethasone intravitreal implant [DEX implant]; Allergan, Inc, Irvine, CA) 0.7 mg combined with laser photocoagulation compared with laser alone for treatment of diffuse diabetic macular edema (DME). DESIGN: Randomized, controlled, multicenter, double-masked, parallel-group, 12-month trial. PARTICIPANTS: Two hundred fifty-three patients with retinal thickening and impaired vision resulting from diffuse DME in at least 1 eye (the study eye) were enrolled. INTERVENTION: Patients were randomized to treatment in the study eye with DEX implant at baseline plus laser at month 1 (combination treatment; n = 126) or sham implant at baseline and laser at month 1 (laser alone; n = 127) and could receive up to 3 additional laser treatments and 1 additional DEX implant or sham treatment as needed. MAIN OUTCOME MEASURES: The primary efficacy variable was the percentage of patients who had a 10-letter or more improvement in best-corrected visual acuity (BCVA) from baseline at month 12. Other key efficacy variables included the change in BCVA from baseline and the area of vessel leakage evaluated with fluorescein angiography. Safety variables included adverse events and intraocular pressure (IOP). RESULTS: The percentage of patients who gained 10 letters or more in BCVA at month 12 did not differ between treatment groups, but the percentage of patients was significantly greater in the combination group at month 1 (P<0.001) and month 9 (P = 0.007). In patients with angiographically verified diffuse DME, the mean improvement in BCVA was significantly greater with DEX implant plus laser treatment than with laser treatment alone (up to 7.9 vs. 2.3 letters) at all time points through month 9 (P ≤ 0.013). Decreases in the area of diffuse vascular leakage measured angiographically were significantly larger with DEX implant plus laser treatment through month 12 (P ≤ 0.041). Increased IOP was more common with combination treatment. No surgeries for elevated IOP were required. CONCLUSIONS: There was no significant between-group difference at month 12. However, significantly greater improvement in BCVA, as demonstrated by changes from baseline at various time points up to 9 months and across time based on the area under the curve analysis, occurred in patients with diffuse DME treated with DEX implant plus laser than in patients treated with laser alone. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Pharmacogenetics for genes associated with age-related macular degeneration in the Comparison of AMD Treatments Trials (CATT).

PURPOSE: To evaluate the pharmacogenetic relationship between genotypes of single nucleotide polymorphisms (SNPs) known to be associated with age-related macular degeneration (AMD) and response to treatment with ranibizumab (Lucentis; Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech) for neovascular AMD. DESIGN: Clinical trial. PARTICIPANTS: Eight hundred thirty-four (73%) of 1149 patients participating in the Comparison of AMD Treatments Trials (CATT) were recruited through 43 CATT clinical centers. METHODS: Each patient was genotyped for SNPs rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3), using TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA). MAIN OUTCOMES MEASURES: Genotypic frequencies were compared with clinical measures of response to therapy at one year, including mean visual acuity (VA), mean change in VA, 15-letter or more increase in VA, retinal thickness, mean change in total foveal thickness, presence of fluid on OCT, presence of leakage on fluorescein angiography (FA), mean change in lesion size, and mean number of injections administered. Differences in response by genotype were evaluated with tests of linear trend calculated from logistic regression models for categorical outcomes and linear regression models for continuous outcomes. To adjust for multiple comparisons, P≤0.01 was considered statistically significant. RESULTS: No statistically significant differences in response by genotype were identified for any of the clinical measures studied. Specifically, there were no high-risk alleles that predicted final VA or change in VA, the degree of anatomic response (fluid on OCT or FA, retinal thickness, change in total foveal thickness, change in lesion size), or the number of injections. Furthermore, a stepwise analysis failed to show a significant epistatic interaction among the variants analyzed; that is, response did not vary by the number of risk alleles present. The lack of association was similar whether patients were treated with ranibizumab or bevacizumab or whether they received monthly or pro re nata dosing. CONCLUSIONS: Although specific alleles for CFH, ARMS2, HTRA1, and C3 may predict the development of AMD, they did not predict response to anti-vascular endothelial growth factor therapy.

Treatment of steroid-induced elevated intraocular pressure with anecortave acetate: a randomized clinical trial.

PURPOSE: The present study is the first randomized clinical trial designed to evaluate the intraocular pressure (IOP)-lowering effect of anecortave acetate (AA) administered at 3 doses (3, 15, or 30 mg) as an anterior juxtascleral depot (AJD) in patients experiencing elevated IOP due to corticosteroid therapy. METHODS: This was a double-masked, randomized, placebo-controlled, multicenter, parallel group trial. Eligible patients had an IOP of at least 24 mmHg and an IOP increase of at least 10 mmHg relative to their IOP before treatment with steroids. A target IOP was established for each patient at baseline. Patients were randomized to 1 of the 4 treatment groups: vehicle, 3 mg AA, 15 mg AA, or 30 mg AA. All patients then received a 0.5 mL AJD of the assigned treatment. Patients returned for scheduled examination visits at weeks 1, 2, 4, 6, months 3, 4, 5, and 6. IOP was measured at each visit as well as best corrected visual acuity (logMAR), ocular motility, eyelid responsiveness, slit lamp examination, and assessment of any adverse events. In addition, at baseline and at exit, a dilated fundus examination was carried out and the lens was examined using LOCS II criteria. RESULTS: Seventy patients were randomized to treatment. At week 4, eyes in the vehicle group showed a 3.4 mmHg (9.1%) decrease from baseline. Reductions for the 3 mg AA (3.1 mmHg, 10.7%) and the 30 mg AA groups (5.4 mmHg, 16.6%) were not significantly different than for vehicle control. However, IOP for the 15 mg AA group at week 4 was reduced 11.5 mmHg (31.3%) from baseline, which was statistically significant (P=0.0487). The mean time to treatment failure was 32.2, 38.9, 56.3, and 32.6 days for the vehicle, 3 mg AA, 15 mg AA, and 30 mg AA groups, respectively. Adverse events were assessed at each post-treatment visit. There were no serious adverse events that were determined to be related to the test article or its administration. CONCLUSIONS: AA can be of benefit to some patients requiring treatment with corticosteroids, but suffering from the side effect of elevated IOP.

Outcomes of birdshot chorioretinopathy treated with an intravitreal sustained-release fluocinolone acetonide-containing device.

PURPOSE: To evaluate outcomes in birdshot chorioretinopathy following intravitreal implantation of a fluocinolone acetonide-containing drug delivery device. DESIGN: Retrospective, multicenter, interventional case study. METHODS: University- and community-based tertiary care. Twenty-two HLA-A29+ birdshot patients (36 eyes) were implanted with a sustained-release corticosteroid device and followed for up to 3 years. Main outcome measures were Snellen acuity, intraocular inflammation, adjunctive therapy, cataract, ocular hypertension, or glaucoma. Paired Wilcoxon statistics were used to analyze visual acuities; paired McNemar statistics were used to analyze presence or absence of other outcomes. RESULTS: Nineteen of 22 patients (32 eyes) completed 12 months of follow-up with improvement in median visual acuity (P=.015). Prior to implantation, 18 of 22 patients (82%) received immunosuppressive therapy versus 1 of 19 (5%) by 12 months (P<.001). Eyes with zero vitreous haze increased from 7 of 27 scored eyes (26%) at baseline to 30 of 30 eyes (100%) by 12 months (P<.001). Cystoid macular edema decreased from 13 of 36 eyes (36%) at baseline to 2 of 32 eyes (6%) at 12 months (P=.006). Five of 24 phakic eyes at baseline exited the study before surgery; all other eyes received cataract surgery. One hundred percent of study eyes had ocular hypertension, required intraocular pressure-lowering therapy, or had glaucoma surgery by 12 months. CONCLUSIONS: Implantation of a fluocinolone acetonide-containing intraocular device in birdshot chorioretinopathy can improve vision, control inflammation, and eliminate systemic therapy. There is a high incidence of cataract progression and intraocular hypertension or glaucoma.

Diagnosis of systemic metastatic retinal lymphoma.

PURPOSE: Systemic metastatic retinal lymphoma (SMRL) is exceptionally rare, as systemic lymphomas most often metastasize to the uvea. We have evaluated a series of SMRL cases to elucidate the clinical and pathological features of SMRL. METHODS: The pathological specimens of intraocular lymphomas (IOLs) at the National Eye Institute from 1991 to 2009 were retrospectively reviewed. These cases were diagnosed by cytology, cytokine measurement (ELISA for interleukin (IL)-10 and IL-6 levels) and Immunoglobulin-Heavy (IgH) and T-cell-receptor (TCR) gene analyses. RESULTS: There were nine B-cell SMRLs (B-SMRL) among 96 B-cell retinal lymphomas (9.4%) and three T-cell SMRLs (T-SMRL) among five T-cell retinal lymphomas (60%) from a total of 116 IOLs, in which 101 were retinal lymphoma. The original sites were nasopharynx (3), testis (2), skin (2), breast (1), blood (1), retroperitoneum (1), ileo-caecum (1) and stomach (1). Cytology of vitreous samples illustrated atypical lymphoma cells with either B- or T-monoclonality. More B-SMRLs had a high ratio of vitreal IL-10 to IL-6 than T-SMRLs. Molecular pathology demonstrated lymphoma cells with gene rearrangements of IgH in all B-SMRLs and TCR in all T-SMRLs. CONCLUSIONS: SMRL and primary retinal lymphoma present with similar clinical manifestations. Systemic T-cell lymphoma invades the retina and vitreous more aggressively than systemic B-cell lymphoma. A diagnosis of SMRL is made when there is a clinical history of systemic lymphoma (particularly from nasopharynx, testis and skin), and lymphoma cells are identified in the vitreous or retina. Molecular analysis is more useful than vitreal cytokine measurement for SMRL diagnosis.

Characterization of sterile intraocular inflammatory responses after intravitreal bevacizumab injection.

PURPOSE: The purpose of this study was to determine the frequency and characteristics of sterile intraocular inflammation occurring after intravitreal bevacizumab (IVB) (Avastin, Genentech, South San Francisco, CA) injection and to analyze whether a repeat IVB or intravitreal ranibizumab (IVR) (Lucentis, Genentech) injection after an episode of postinjection inflammation elicits a repeat inflammatory reaction. METHODS: A retrospective case series evaluated 16,166 IVB injections administered between 2006 and 2008. Patients with postinjection inflammation were analyzed for the number of previous injections, time from prior injection to incident injection, presenting signs and symptoms, treatment, visual acuity, time from onset to resolution and recovery of vision, and whether repeat injection caused recurrent inflammation. RESULTS: The incidence of sterile intraocular inflammation after IVB injection resolving with topical antibiotics and steroids alone was 0.27% (44 of 16,166). The average number of prior IVB injections in the ipsilateral eye was 2.8 ± 0.4 with 10 cases occurring with first-time injections. The average time from injection to recovery of visual acuity was 53 ± 18 days, and from injection to resolution of inflammation was 37 ± 5 days. Thirty-six cases received subsequent IVB or intravitreal ranibizumab, and there were three episodes of recurrent inflammation with repeat IVB. The average follow-up was 17 ± 1 month. CONCLUSION: In most cases of sterile intraocular inflammation after IVB, visual acuity returned to baseline, and intraocular inflammation rarely recurred with repeat IVB or intravitreal ranibizumab.

Vitreous metastases of primary cutaneous B-cell lymphoma.

PURPOSE: To describe two cases of vitreous metastases of primary cutaneous B-cell lymphoma (PCBCL). METHODS: Observational case series. RESULTS: A 73-year-old man and an 81-year-old woman, both with a history of PCBCL, diffuse large cell type, presented with decreased visual acuity due to vitritis. Both patients underwent vitreous biopsy that demonstrated B-cell lymphoma, large cell type, and confirmed metastases of cutaneous B-cell lymphoma to the vitreous. CONCLUSION: PCBCL, diffuse large cell type, is a rare form of non-Hodgkin lymphoma that can metastasize to the vitreous without visible chorioretinal involvement.

The role of difluprednate ophthalmic emulsion in clinical practice.

The mainstay in the treatment of ocular inflammation, either post-surgical or endogenous, is the use of steroids. While these agents effectively address inflammation, they are not without their risks, including ocular hypertension and acceleration of cataract formation. The most notorious culprits are the strong steroids, such as prednisolone acetate and betamethasone. This review aims to cover the biochemistry and drug development of difluprednate, a novel synthetic strong steroid emulsion. In vivo pharmacokinetics as well as ocular distribution and metabolism are discussed, followed by a comprehensive summary of phase I, II, and III clinical trials evaluating safety and efficacy in patients suffering from postoperative inflammation or anterior uveitis. The objective is to provide an increased familiarity with this newly approved medication as a welcome addition to the ophthalmologist's armamentarium.

Reduction of intraocular pressure with anecortave acetate in eyes with ocular steroid injection-related glaucoma.

OBJECTIVE: To evaluate the intraocular pressure (IOP)-lowering potential of anecortave acetate (AA) in eyes with steroid-related ocular hypertension inadequately controlled with the maximal tolerated or appropriate medical therapy. DESIGN: Uncontrolled case series. METHODS: A total of 8 eyes of 7 subjects with medically uncontrolled IOP following intravitreal or sub-Tenon injections of triamcinolone acetonide were included. All received an 0.8-mL anterior juxtascleral depot of 3% AA solution (24 mg) under topical anesthesia. The IOP was assessed weekly for the first month, then monthly for a minimum of 1 year. RESULTS: The mean baseline IOP was 39.9 mm Hg. After 1 week, the mean IOP decreased 12 mm Hg (29%; P = .005) and by 1 month, the mean IOP had decreased 14.1 mm Hg (34.5%; P = .003) from baseline. Four eyes required surgical intervention despite a decrease in IOP because of markedly elevated initial IOP and the degree of preexisting glaucomatous optic neuropathy. We observed no adverse events. CONCLUSIONS: An anterior juxtascleral depot of AA lowers IOP substantially in some eyes with medically uncontrolled steroid-related ocular hypertension. Further study is warranted to clarify the role of AA in treating this condition as well as other forms of glaucoma.

Treatment of posterior uveitis with a fluocinolone acetonide implant: three-year clinical trial results.

OBJECTIVES: To evaluate the safety and efficacy of 0.59-mg and 2.1-mg fluocinolone acetonide (FA) intravitreous implants in noninfectious posterior uveitis. DESIGN: A 3-year, multicenter, randomized, historically controlled trial of the 0.59-mg FA intravitreous implant in 110 patients and the 2.1-mg FA intravitreous implant in 168 patients. MAIN OUTCOME MEASURES: Recurrence rate, vision, and complications. RESULTS: Uveitis recurrence was reduced in implanted eyes from 62% (during the 1-year preimplantation period) to 4%, 10%, and 20% during the 1-, 2-, and 3-year postimplantation periods, respectively, for the 0.59-mg dose group (P < .01) and from 58% to 7%, 17%, and 41%, respectively, for the 2.1-mg dose group (P < .01). More implanted eyes than nonimplanted eyes had improved visual acuity (P < .01). Implanted eyes had higher incidences of intraocular pressure elevation (> or = 10 mm Hg) than nonimplanted eyes (P < .01), and glaucoma surgery was required in 40% of implanted eyes vs 2% of nonimplanted eyes (P < .01). Cataracts were extracted in 93% of phakic implanted eyes vs 20% of phakic nonimplanted eyes (P < .01). CONCLUSIONS: The FA implant significantly reduced uveitis recurrence and improved or stabilized visual acuity in subjects with noninfectious posterior uveitis. Most subjects required cataract extraction, and a significant proportion required intraocular pressure-lowering surgery. APPLICATION TO CLINICAL PRACTICE: The FA implant provides an alternative therapy for prolonged control of inflammation in noninfectious posterior uveitis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00407082.

Intraocular pressure in patients with uveitis treated with fluocinolone acetonide implants.

OBJECTIVE: To report the incidence and management of elevated intraocular pressure (IOP) in patients with uveitis treated with the fluocinolone acetonide (FA) intravitreal implant. DESIGN: Pooled data from 3 multicenter, double-masked, randomized, controlled, phase 2b/3 clinical trials evaluating the safety and efficacy of the 0.59-mg or 2.1-mg FA intravitreal implant or standard therapy were analyzed. RESULTS: During the 3-year follow-up, 71.0% of implanted eyes had an IOP increase of 10 mm Hg or more than baseline and 55.1%, 24.7%, and 6.2% of eyes reached an IOP of 30 mm Hg or more, 40 mm Hg or more, and 50 mm Hg or more, respectively. Topical IOP-lowering medication was administered in 74.8% of implanted eyes, and IOP-lowering surgeries, most of which were trabeculectomies (76.2%), were performed on 36.6% of implanted eyes. Intraocular pressure-lowering surgeries were considered a success (postoperative IOP of 6-21 mm Hg with or without additional IOP-lowering medication) in 85.1% of eyes at 1 year. The rate of hypotony (IOP

Comparison of the modified Early Treatment Diabetic Retinopathy Study and mild macular grid laser photocoagulation strategies for diabetic macular edema.

OBJECTIVE: To compare 2 laser photocoagulation techniques for treatment of diabetic macular edema: the modified Early Treatment Diabetic Retinopathy Study (ETDRS) direct/grid photocoagulation technique and a potentially milder (but potentially more extensive) mild macular grid (MMG) laser technique in which microaneurysms are not treated directly and small mild burns are placed throughout the macula, whether or not edema is present. METHODS: Two hundred sixty-three subjects (mean age, 59 years) with previously untreated diabetic macular edema were randomly assigned to receive laser photocoagulation by either the modified ETDRS (162 eyes) or MMG (161 eyes) technique. Visual acuity, fundus photographs, and optical coherence tomography measurements were obtained at baseline and at 3.5, 8, and 12 months. Treatment was repeated if diabetic macular edema persisted. MAIN OUTCOME MEASURE: Change in optical coherence tomography measurements at 12-month follow-up. RESULTS: Among eyes with a baseline central subfield thickness of 250 microm or greater, central subfield thickening decreased by an average of 88 microm in the modified ETDRS group and by 49 microm in the MMG group at 12-month follow-up (adjusted mean difference, 33 microm; 95% confidence interval, 5-61 microm; P = .02). Weighted inner zone thickening by optical coherence tomography decreased by 42 microm in the modified ETDRS group and by 28 microm in the MMG group (adjusted mean difference, 14 microm; 95% confidence interval, 1-27 microm; P = .04); maximum retinal thickening (maximum thickening of the central and 4 inner subfields) decreased by 66 and 39 microm, respectively (adjusted mean difference, 27 microm; 95% confidence interval, 6-47 microm; P = .01), and retinal volume decreased by 0.8 and 0.4 mm3, respectively (adjusted mean difference, 0.3 mm3; 95% confidence interval, 0.02-0.53 mm3; P = .03). At 12 months, the mean change in visual acuity was 0 letters in the modified ETDRS group and 2 letters worse in the MMG group (adjusted mean difference, 2 letters; 95% confidence interval, -0.5 to 5 letters; P = .10). CONCLUSIONS: At 12 months after treatment, the MMG technique was less effective at reducing optical coherence tomography-measured retinal thickening than the more extensively evaluated current modified ETDRS laser photocoagulation approach. However, the visual acuity outcome with both approaches is not substantially different. Given these findings, a larger long-term trial of the MMG technique is not justified. APPLICATION TO CLINICAL PRACTICE: Modified ETDRS focal photocoagulation should continue to be a standard approach for treating diabetic macular edema. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00071773.

The white dot syndromes.

PURPOSE: To review the distinctive and shared features of the white dot syndromes, highlighting the clinical findings, diagnostic test results, proposed etiologies, treatments, and prognosis. DESIGN: Review. METHODS: Review of the literature. RESULTS: Common white dot syndromes are reviewed, including acute posterior multifocal placoid pigment epitheliopathy, birdshot chorioretinopathy, diffuse unilateral subacute neuroretinitis, multiple evanescent white dot syndrome, multifocal choroiditis with panuveitis, serpiginous choroiditis, and acute zonal occult outer retinopathy. CONCLUSIONS: The white dot syndromes are a group of disorders characterized by multiple whitish-yellow inflammatory lesions located at the level of the outer retina, retinal pigment epithelium, and choroid. For clinicians and researchers alike, they present significant diagnostic and therapeutic challenges.