Vitreous Haze Research Articles

Intravitreal Adalimumab in Active Noninfectious Uveitis: A Pilot Study

Purpose: To evaluate the short-term efficacy of intravitreal adalimumab (IVA) for the treatment of eyes with active noninfectious uveitis.Methods: Consecutive eyes with active noninfectious uveitis were injected with IVA at 0, 2, then every 4 weeks for total of 26 weeks.Results: Six out of 7 patients (12 of 13 eyes) completed 26 weeks of treatment. One patient (1 eye) failed treatment. Seven out of 12 eyes had improvement of ≥2 ETDRS lines. Three out of three eyes had resolution of anterior chamber cells. And 9 of 10 eyes with vitreous haze had zero haze at 26 weeks. Five out of 8 eyes with macular edema had complete resolution. Median fluorescein angiography score improved from 14 to 4 on last follow-up.Conclusions: IVA was effective in controlling the inflammation, decreasing the macular edema, and improving the best corrected visual acuity in the majority of eyes in this series.

Fast and Successful Management of Intraocular Inflammation with a Single Intravitreal Dexamethasone Implant

Purpose: To investigate the efficacy and safety of a single dexamethasone intravitreal implant (Ozurdex®, 700 µg). Methods: In this prospective noncomparative case series, 84 patients (54 females) received a dexamethasone intravitreal implant. At weeks 4, 12 and 24 after the injection, vitreous haze, macular thickness and best corrected visual acuity (BCVA) were assessed and adverse events reported. Results: Clearance of vitreous haze could be achieved after 4 weeks in 61% of all eyes (p < 0.001) and remained significant until week 24 (p < 0.001). This was paralleled by a reduction of central retinal thickness after 4 (p < 0.001), 12 (p < 0.001) and 24 weeks (p < 0.006). Significant and fast improvement of BCVA was already achieved after 4 weeks (p < 0.001) but vanished by week 24. Intraocular pressure reached ≥35 mm Hg in 3 eyes and was significantly more frequent in intermediate uveitis compared to posterior uveitis (p < 0.016). Conclusions: The dexamethasone implant is effective in controlling intraocular posterior segment inflammation and reduces central retinal thickness fast and effectively.

Measurement Reliability of Axial Length of the Human Eye by using Partial Coherence Interferometry

To investigate the minimum near-infrared ray intensity required (quantifiable threshold value) for consistent measurements of axial length (AL) using partial coherence interferometry (PCI), we attached two polarizing lenses (PL) to two types of PCI (IOLmaster, ALscan). The near-infrared ray intensity of PCI was modified by rotating the axis of one PL at intervals of 5 degrees. The right eye of each volunteer was measured three times and the AL and signal-to-noise ratio (SNR) was recorded five times for each measurement. Reduction of light intensity was theoretically estimated using Malus' Law. AL was measured consistently with both IOLmaster and ALscan until they reached 55 degrees (1.33 % of intensity) and 60 degrees (0.77%), respectively (P = 0.343, Log-rank test). In contrast, SNR decreased as light intensity decreased. In addition, to analyze media opacities that precluded measurement of AL, we retrospectively reviewed the medical records of patients unmeasurable by PCI (ALscan) from May to November 2013. Thirty-eight of 473 eyes (8.0%) could not be measured using ALscan due to media opacities, such as severe posterior subcapsular cataract (PSC, 11 eyes), hypermature cataract (9 eyes), and vitreous hemorrhage (18 eyes). The mean grades of vitreous haze and PSC were <TEX>$7.72{\pm}0.96$</TEX> and <TEX>$4.45{\pm}1.04$</TEX>, respectively. In conclusion, up to 0.77-1.33% of near-infrared rays decreased, and AL could be measured consistently.

Certolizumab Pegol, a New Anti-TNF-α in the Armamentarium against Ocular Inflammation

Purpose: To study the efficacy and tolerance of certolizumab pegol (CZP) in active uveitis.Methods: Retrospective case series at 4 referral centers. Patients treated with CZP for active uveitis during at least 6 months were eligible. Inflammation by SUN scores, visual acuity (VA) (logMAR), and central macular thickness (CMT) were compared from baseline until final follow-up. Quiescence was defined as 0+ to 0.5+ in anterior chamber and vitreous haze scores and no CMT increase.Results: Four males and 3 females (14 eyes) were included, mean age 42.4 ± 8.8 years. All were long-lasting chronic-relapsing uveitis with prior failure to other anti-TNF-α. After a mean follow-up of 10.4 ± 4.8 months, 5/7 patients (71.4%) achieved quiescence with CZP. VA improved significantly from +0.52 ± 0.68 to +0.45 ± 0.68 (p = 0.032) at 1 month and to +0.44 ± 0.64 (p = 0.035) at 6 months. No adverse events were found.Conclusion: CZP can be an effective alternative in refractory uveitis.

Multicenter Study of Intravitreal Dexamethasone Implant in Noninfectious Uveitis: Indications, Outcomes, and Reinjection Frequency

To identify clinical outcomes and treatment patterns of intravitreal dexamethasone implant (Ozurdex; Allergan, Inc) in noninfectious uveitis in the clinical setting. Multicenter retrospective cohort study. Eighty-two eyes (63 patients) receiving 142 implant injections over 35 months were included. Treatment indication, uveitis diagnosis, visual acuity, intraocular pressure, vitreous haze score, central retinal thickness by optical coherence tomography, phakic status, number of injections, time to reinjection, systemic treatments, and complications data were collected. Time to visual acuity and vitreous haze score improvement as per the Standardization of Uveitis Nomenclature guidelines were also determined. The probability of visual acuity improvement (≥0.3 logarithm of the minimal angle of resolution units improvement) was 39% at 1 month, 49% at 3 months, 52% at 6 months, and 58% at 12 months. Eyes with baseline vitritis (vitreous haze score ≥+0.5, n = 45) had a probability of vitreous haze score improvement (2-step decrease or change from +0.5 to 0) at 2 weeks of 41%, at 1 month 63%, at 3 months 73%, at 6 months 79%, and at 12 months 88%. In eyes that completed 12-month follow-up (n = 54), 40.7% underwent 2 injections (mean time to second injection of 6.6 ± 1.9 months) and 11.2% required ≥3 injections (mean time to third injection of 11 ± 1.5 months). Dexamethasone implant use in uveitis provides favorable visual acuity and vitreous haze score outcomes but requires repeated injections, an important consideration when choosing intraocular treatment as a route to controlling uveitis.

Changes in vitreous haze over time with intravitreal sirolimus in noninfectious posterior‐segment uveitis (NI‐PSU): results of SAKURA Study 1

AbstractPurpose To evaluate changes in vitreous haze (VH) scores over time in in SAKURA Study 1, a randomized, double‐masked, multicenter, international phase III study of subjects with active NI‐PSU.Methods 347 subjects with active NI‐PSU (VH score ≥1.5+) were randomized to intravitreal sirolimus (44, 440, or 880 µg), given every 2 months. VH scores were assessed at Week 2 and Months 1–5.Results At baseline, the mean (SD) VH scores were 1.9 (0.44) for the 440 µg group and 1.9 (0.50) for the 44 µg group. The risk:benefit profile was most favorable with 440 µg: Significantly more patients achieved a VH score of 0 at Month 5 (the primary endpoint) with 440 µg vs 44 µg (22.8% vs 10.3%; p=.025). 440 µg was also significantly more effective than 44 µg in achieving a VH score of 0/0.5+ (51.8% vs 35%; p=.012). Improvement was seen as early as Week 2 with 440 µg (22.8% with VH=0/0.5+) and continued improvement with this dose was seen at every analysis visit (36.0%, 40.4%, 49.1%, 42.1%, and 51.8% with VH=0/0.5+ at Months 1–5, respectively).Conclusion Intravitreal sirolimus 440 μg significantly improved inflammation in this diverse NI‐PSU population. VH improvement was seen as early as 2 weeks after the first injection and continued through Month 5. Treatment with intravitreal sirolimus 440 µg appears to be effective in treating NI‐PSU, with a balanced safety profile. Commercial interest

Classification of uveitis

AbstractClassification and standardization of uveitis is important, as it enhances the precision and comparability of clinical research from different centers and assists in the development of a complete picture of the course of the disorders and their response to treatment. Attempts have been made to standardize some aspects of uveitis, and various classification criteria, inflammation grading schema, and outcomes criteria have been described. The most widely used classification of uveitis is the one devised by the International Uveitis Study Group (IUSG) in 1987, based on the anatomical location of the inflammation. This classification includes anterior uveitis (iritis, iridocyclitis, and anterior cyclitis), intermediate uveitis (pars planitis, posterior cyclitis, and hyalitis), posterior uveitis (focal, multifocal, or diffuse choroiditis, chorioretinitis, retinitis, and neuroretinitis) or panuveitis (anterior chamber, vitreous, retina, and choroid). In 2005, the Standardization of Uveitis Nomenclature (SUN) Working Group standardized a grading schema for aspects of intraocular intraocular inflammation, that is, anterior chamber cells, anterior chamber flare, and vitreous haze, was developed. Standardized definitions of outcomes, including reporting visual acuity outcomes, were approved. Today’s uveitis nomenclature has been revised regarding the anatomical location and the grade of inflammation, and supplemented by the inclusion of definitions for onset, duration and course.

The effect of intravitreal adalimumab on the treatment of active noninfectious ocular inflammation: A pilot study

AbstractPurpose To evaluate the short term efficacy of intravitreal adalimumab (IVA) for the treatment of eyes with active noninfectious uveitis.Methods In a prospective noncomparative interventional case series, consecutive eyes with active noninfectious uveitis were injected with IVA at 0, 2 then every 4 weeks for total of 6 months. Change in VA, grade of inflammation (cells, haze, leakage on FA adopted from the angiography scoring for uveitis working group), and central retinal thickness (CRT) were recorded. No systemic or ocular therapies were added to the IVA treatment during the study period.Results Six out of seven patients (12 of 13 eyes) completed 26 weeks of treatment. One patient (1 eye) failed treatment. Median logMar VA at baseline was 0.243 and improved to 0.049 at 26 weeks. Seven out of twelve eyes had improvement of ≥2 ETDRS lines. All three eyes with anterior chamber cells grade ≥1 at baseline had zero cells at 26 weeks. Also, all nine eyes with vitreous haze grade ≥1 at baseline had zero haze on last follow up. Median CRT at baseline was 317 microns and decreased to 277 microns. Five out of eight eyes with macular edema had complete resolution. Median FA score at baseline was 14 and improved to 4. Using Wilcoxon Signed Rank test, the decrease in logMar, CRT and FA score at 26 weeks compared to baseline was significant (n=12 eyes; p=0.003, 0.021, 0.002 respectively). No local or systemic side effects were detected. Stratifying the data to include one eye per patient revealed similar results.Conclusion IVA was safe in this pilot study; was effective in improving the VA in 7/12 eyes, resolving macular edema in 5/8 eyes &amp; decreasing AC cells, vit haze and FA score in 12 eyes while 1 patient (1 eye) failed treatment.

Correlation between clinical signs and optical coherence tomography with enhanced depth imaging findings in patients with birdshot chorioretinopathy.

Birdshot chorioretinopathy (BCR) is a bilateral posterior uveitis that typically requires aggressive therapy to prevent loss of vision. Clinical signs of disease activity may be subtle and visual acuity is often preserved despite significant loss of visual function. Optical coherence tomography with enhanced depth imaging (OCT-EDI), a new technology that allows visualization of structures posterior to the retinal pigment epithelium, may be a useful tool to monitor disease activity in these patients. To determine the correlation between symptoms and signs of disease activity in BCR and specific findings on OCT-EDI. Retrospective medical record review of 14 patients treated for BCR in the uveitis clinic at Northwestern University. All patients underwent OCT-EDI (58 scans). Clinical symptoms of photopsias/vibrating vision and signs of macular edema, vitreous haze, and retinal vasculitis were graded; a second grading scale was developed for the evaluation of OCT-EDI. Individual scans of each eye of each patient at each point were graded in a masked fashion. Optical coherence tomography with EDI in BCR. Spearman rank correlation of clinical measures to OCT-EDI measures. The most frequent score in each clinical category was 0 (inactive). In those BCR patients with symptoms (21 eye examinations), the subjective complaint of photopsias/vibrating vision was associated with the objective finding of suprachoroidal fluid on OCT-EDI (P = .003), and the frequency and severity of photopsias correlated with the thickness of the fluid band (Pearson product moment correlation, 0.39). Two of the clinical markers of disease activity measured in this study (vasculitis and vitreous haze) also showed a significant Spearman rank correlation with the presence and amount of suprachoroidal fluid on OCT-EDI (vasculitis, 0.45 [P < .001]; vitreous haze, 0.59 [P < .001]). The presence of suprachoroidal fluid on OCT-EDI appears to correlate with the subjective complaints of photopsias in patients with BCR and other more easily assessed clinical features such as vasculitis and vitreous haze. Optical coherence tomography with EDI may be a useful tool for objective monitoring of BCR.

A Randomized Clinical Trial Comparing Methotrexate and Mycophenolate Mofetil for Noninfectious Uveitis

To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Multicenter, block-randomized, observer-masked clinical trial. Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31). There was no statistically significant difference in corticosteroid-sparing control of inflammation between patients receiving methotrexate or mycophenolate mofetil. However, there was a 22% difference in treatment success favoring methotrexate.

Objective Measurement of Vitreous Inflammation Using Optical Coherence Tomography

To obtain measurements of vitreous signal intensity from optical coherence tomography (OCT) image sets in patients with uveitis, with the aim of developing an objective, quantitative marker of inflammatory activity in patients with this disease. Retrospective, observational case-control series. Thirty patients (30 eyes) with vitreous haze secondary to intermediate, posterior, or panuveitis; 12 patients (12 eyes) with uveitis but without evidence of vitreous haze; and 18 patients (18 eyes) without intraocular inflammation or vitreoretinal disease. Clinical and demographic characteristics were recorded, including visual acuity (VA), diagnosis, and anatomic type of uveitis. In each eye, the anterior chamber (AC) was graded for cellular activity and flare according to standardized protocols. The presence and severity of vitreous haze were classified according to the National Eye Institute system. Spectral-domain OCT images were analyzed using custom software. This software provided an "absolute" measurement of vitreous signal intensity, which was then compared with that of the retinal pigment epithelium (RPE), generating an optical density ratio with arbitrary units ("VIT/RPE-Relative Intensity"). Correlation between clinical vitreous haze scores and OCT-derived measurements of vitreous signal intensity. The VIT/RPE-Relative Intensity was significantly higher in uveitic eyes with known vitreous haze (0.150) than in uveitic eyes without haze or in healthy controls (0.0767, P = 0.0001). The VIT/RPE-Relative Intensity showed a significant, positive correlation with clinical vitreous haze scores (r = 0.566, P = 0.0001). Other ocular characteristics significantly associated with VIT/RPE-Relative Intensity included VA (r = 0.573, P = 0.0001), AC cells (r = 0.613, P = 0.0001), and AC flare (r = 0.385, P = 0.003). Measurement of VIT/RPE-Relative Intensity showed a good degree of intergrader reproducibility (95% limits of agreement, -0.019 to 0.016). These results provide preliminary evidence that OCT-derived measurements of vitreous signal intensity may be useful as an outcome measure in patients with uveitis. If validated in future studies, such measures may serve as an objective, quantitative disease activity end point, with the potential to improve the "signal:noise" ratio of clinical trials in this area, thus enabling smaller studies for the same power. The incorporation of automated vitreous analysis in commercial OCT systems may, in turn, facilitate monitoring and re-treatment of patients with uveitis in clinical practice.

Presumed toxoplasmic central retinal artery occlusion and multifocal retinitis with perivascular sheathing

Central retinal artery occlusion (CRAO) and multifocal retinitis with perivascular sheathing are rare in ocular toxoplasmosis. We report a case of toxoplasmic CRAO and multifocal retinitis with perivascular sheathing. A healthy 83-year-old male developed left panuveitis. Funduscopic examination of the left eye showed a swollen optic disc and sheathing of the retinal artery with a dense vitreous haze and a white retinal lesion. Serum anti-toxoplasma antibodies were positive in a latex agglutination assay. Vitrectomy was performed to improve visualization of the retinal lesions and for examination of causative microorganisms. A postoperative fundus examination revealed CRAO with optic disc involvement and multifocal retinitis with perivascular sheathing. Qualitative multiplex polymerase chain reaction detected the Toxoplasma gondii B1 gene in ocular fluid from both the aqueous and vitreous humor. The presumed diagnosis of ocular toxoplasmosis was made and treatment was started with prednisone and acetylspiramycin with subsequent improvement. Two months later, the patient developed active retinochoroiditis in the left eye. After 6 weeks of anti-toxoplasma therapy, the disease involuted. Retinal vascular occlusions and multifocal retinitis with perivascular sheathing are rare in toxoplasmosis. This is the first case report of toxoplasmic CRAO and multifocal retinitis with perivascular sheathing. The diagnosis of ocular toxoplasmosis should be considered in patients with retinal artery occlusions and multifocal retinitis with perivascular sheathing associated with inflammation.

Interobserver Agreement in Clinical Grading of Vitreous Haze Using Alternative Grading Scales

To evaluate the reliability of clinical grading of vitreous haze using a new 9-step ordinal scale versus the existing 6-step ordinal scale. Evaluation of diagnostic test (interobserver agreement study). A total of 119 consecutive patients (204 uveitic eyes) presenting for uveitis subspecialty care on the study day at 1 of 3 large uveitis centers. Five pairs of uveitis specialists clinically graded vitreous haze in the same eyes, one after the other using the same equipment, using the 6- and 9-step scales. Agreement in vitreous haze grade between each pair of specialists was evaluated by the κ statistic (exact agreement and agreement within 1 or 2 grades). The scales correlated well (Spearman's ρ = 0.84). Exact agreement was modest using both the 6-step and 9-step scales: average κ = 0.46 (range, 0.28-0.81) and κ = 0.40 (range, 0.15-0.63), respectively. Within 1-grade agreement was slightly more favorable for the scale with fewer steps, but values were excellent for both scales: κ = 0.75 (range, 0.66-0.96) and κ = 0.62 (range, 0.38-0.87), respectively. Within 2-grade agreement for the 9-step scale also was excellent (κ = 0.85; range, 0.79-0.92). Two-fold more cases were potentially clinical trial eligible on the basis of the 9-step than the 6-step scale (P<0.001). Both scales are sufficiently reproducible using clinical grading for clinical and research use with the appropriate threshold (≥ 2- and ≥ 3-step differences for the 6- and 9-step scales, respectively). The results suggest that more eyes are likely to meet eligibility criteria for trials using the 9-step scale. The 9-step scale appears to have higher reproducibility with Reading Center grading than clinical grading, suggesting that Reading Center grading may be preferable for clinical trials.

Treatment with Repeat Dexamethasone Implants Results in Long-Term Disease Control in Eyes with Noninfectious Uveitis

To describe the long-term outcome of eyes with uveitis after repeated treatment with dexamethasone implants (Ozurdex; Allergan, Inc., Irvine, CA). Retrospective, observational case series. Thirty-eight eyes of 27 patients with uveitis that were treated with 61 dexamethasone implants. All eyes underwent dexamethasone pellet implantation. Anatomic and functional outcomes, as well as ocular complications, were noted. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), vitreous haze score, and presence of increased intraocular pressure or cataract. Average follow-up was 17.3 ± 1.8 months after the first implant (median, 13.3 months; range, 3-54.5 months; 54.65 eye-years), with 14 eyes (36.9%) receiving a single implant and 24 eyes (63.1%) receiving multiple implantations. After the first implantation, average BCVA improved significantly from 0.47 ± 0.05 logarithm of the minimum angle of resolution (logMAR) units (Snellen equivalent, 20/60) to 0.27 ± 0.07 logMAR (Snellen equivalent, 20/37; P<0.001); CRT decreased by 263 ± 44.22 μm (P = 0.003), although macular edema persisted in 50% of eyes, and the percentage of eyes achieving a vitreous haze score of 0 increased from 58% to 83% (P = 0.03). The median duration of therapeutic effect after the first injection was 6 months (range, 2-42 months), with a similar response achieved after each repeat implantation. The accumulated effect of repeat dexamethasone implants resulted in a continued improvement in BCVA (R(2) = 0.91; P<0.0001), with significant improvement and stabilization of CRT. After repeated implantations, 2 eyes had progression of posterior subcapsular opacities, although neither required surgery. There were 7 instances of increased intraocular pressure of more than 21 mmHg at a rate of 0.13 per eye-year, all of which responded to pharmacologic treatment. The accumulated effect of repeat dexamethasone pellet implantations improves retinal thickness and resolves ocular inflammation, resulting in restoration of ocular function. Ocular complications were minimal, with no eyes requiring surgery for increased ocular pressure or progression of cataract.

Adverse Effects and Short-term Results After Selective Laser Trabeculoplasty

To evaluate the risk of adverse effects and to demonstrate short-term results after selective laser trabeculoplasty (SLT) in glaucoma patients. Sixty-four eyes of 64 patients with primary open-angle glaucoma, not sufficiently treated with local antiglaucomatous therapy, were included in this prospective study. Intraocular pressure (IOP), anterior chamber cells, anterior chamber flare, and vitreous haze (according to the Standardization of Uveitis Nomenclature Working Group) were examined before SLT, for 24 hours, 14 days, 6 weeks, and 3 months after laser. Furthermore, macular thickness measurements in 9 Early Treatment Diabetic Retinopathy Study subfields, including central subfield, measured by Spectralis OCT were performed. The differences between prelaser and postlaser values were obtained. The average of mean preoperative IOP measurement was 19.1±3.972 mm Hg compared with 12.9±2.513 (P<0.001), 13.2±3.331 (P<0.001), 14.1±2.731 (P<0.001), and 13.9±2.922 mm Hg (P<0.001) 24 hours, 14 days, 6 weeks, and 3 months post-SLT, respectively. The central subfield preoperatively was 278.14±74.355 µm compared with 277.14±71.461 (P=0.177), 277.14±71.461 (P=0.354), 287.34±74.363 (P=0.414), and 257.45±68.431 µm (P=0.214) 24 hours, 14 days, 6 weeks, and 3 months after treatment. Anterior chamber cells, anterior chamber flare, and vitreous haze were not denoted at any time of examination. In this study, no significant increase in macular thickness and no other adverse effects were present. Furthermore, SLT was found to significantly lower IOP in glaucoma patients in addition to local therapy. In conclusion, SLT has a good ability to reduce IOP with a minor risk of adverse effects.

Incidence of Visual Improvement in Uveitis Cases with Visual Impairment Caused by Macular Edema

Among cases of visually significant uveitic macular edema (ME), to estimate the incidence of visual improvement and identify predictive factors. Retrospective cohort study. Eyes with uveitis, seen at 5 academic ocular inflammation centers in the United States, for which ME was documented to be currently present and the principal cause of reduced visual acuity (<20/40). Data were obtained by standardized chart review. Decrease of ≥ 0.2 base 10 logarithm of visual acuity decimal fraction-equivalent; risk factors for such visual improvement. We identified 1510 eyes (of 1077 patients) with visual impairment to a level <20/40 attributed to ME. Most patients were female (67%) and white (76%), and had bilateral uveitis (82%). The estimated 6-month incidence of ≥ 2 lines of visual acuity improvement in affected eyes was 52% (95% confidence interval [CI], 49%-55%). Vision reduced by ME was more likely to improve by 2 lines in eyes initially with poor visual acuity (≤ 20/200; adjusted hazard ratio [HR] 1.5; 95% CI, 1.3-1.7), active uveitis (HR, 1.3; 95% CI, 1.1-1.5), and anterior uveitis as opposed to intermediate (HR, 1.2), posterior (HR, 1.3), or panuveitis (HR, 1.4; overall P = 0.02). During follow-up, reductions in anterior chamber or vitreous cellular activity or in vitreous haze each led to significant improvements in visual outcome (P <0.001 for each). Conversely, snowbanking (HR, 0.7; 95% CI, 0.4-0.99), posterior synechiae (HR, 0.8; 95% CI, 0.6-0.9), and hypotony (HR, 0.2; 95% CI, 0.06-0.5) each were associated with lower incidence of visual improvement with respect to eyes lacking each of these attributes at a given visit. These results suggest that many, but not all, patients with ME causing low vision in a tertiary care setting will enjoy meaningful visual recovery in response to treatment. Evidence of significant ocular damage from inflammation (posterior synechiae and hypotony) portends a lower incidence of visual recovery. Better control of anterior chamber or vitreous activity is associated with a greater incidence of visual improvement, supporting an aggressive anti-inflammatory treatment approach for ME cases with active inflammation.

Validity and Agreement of Uveitis Experts in Interpretation of Ocular Photographs for Diagnosis of Behçet Uveitis

Purpose: To evaluate agreement and estimate sensitivity and specificity of uveitis specialists' interpretation of ocular photographs in diagnosing Behçet uveitis.Methods: Fourteen Turkish uveitis specialists, masked to demographic and clinical features of patients, independently labeled ocular photographs (29 Behçet/30 other diagnoses) as “Behçet uveitis” or “non-Behçet.” Level of agreement was evaluated using kappa statistics. Photographs were categorized based on ocular signs captured and performance of observers.Results: Exact agreement with the correct diagnosis was 56–81%. Seven reviewers correctly labeled more than 70% of photographs. Interobserver agreement among those 7 reviewers revealed moderate (κ = 0.41–0.60) or substantial (κ = 0.61–0.80) agreement in 76% of pairs. Smooth layered hypopyon, superficial retinal infiltrate with retinal hemorrhages, and branch retinal vein occlusion with vitreous haze were correctly recognized as Behçet uveitis by majority of reviewers.Conclusions: There are ocular signs of Behçet disease that can be considered diagnostic even in the absence of any other clinical information.

Risk factors associated with the relapse of uveitis in patients with juvenile idiopathic arthritis: a preliminary report

To identify risk factors associated with relapse of uveitis in patients with recurrent uveitis associated with juvenile idiopathic arthritis (JIA) after treatment with immunomodulatory therapy (IMT) and durable remission of 1 year. The medical records of 30 patients with JIA-associated uveitis who were successfully treated with IMT to a state of corticosteroid-free remission and subsequently remained in remission after discontinuation of IMT for a period of at least 1 year were retrospectively reviewed. In subsequent follow-up, some patients had relapse of uveitis, whereas others continued to be in remission. Remission was defined as <1 + cells in the anterior chamber and <1 + vitreous haze grading; relapse was defined as ≥ 1 + cell in the anterior chamber or ≥ 1 + vitreous haze grading. A total of 30 patients were included. Of these, 17 (56.7%) patients remained in uveitic remission, whereas 13 (43.3%) relapsed. The patients in remission received IMT earlier in the course of disease compared with patients who relapsed (median, 12 months vs 72 months; P = 0.002 [Mann-Whitney test]). Patients in remission had received treatment with IMT at a younger age compared with the relapse group (median age, 7 years vs 13 years; P = 0.02 [Mann-Whitney test]). None of the other factors studied revealed a statistically significant association. Patients with JIA-associated uveitis who were treated with IMT earlier in the course of disease and at a younger age were associated with a lower rate of relapse of uveitis after durable remission and 1 year of quiescence, compared with similar patients who relapsed.

Psychometric evaluation of the National Eye Institute Visual Function Questionnaire and Visual Function Questionnaire Utility Index in patients with non-infectious intermediate and posterior uveitis

To evaluate the psychometric properties of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) and Visual Function Questionnaire Utility Index (VFQ-UI) in patients with non-infectious intermediate and posterior uveitis. Secondary analysis of pooled data from a 26-week, multicenter, masked, randomized, sham-controlled Phase 3 clinical trial. Health-related quality of life was assessed using the NEI VFQ-25, the EQ-5D, and SF-36. Internal consistency reliability, reproducibility, convergent validity, and known groups of BCVA and vitreous haze severity were assessed. Clinically significant difference was assessed using anchor-based and distribution-based methods. The study included 224 subjects with non-infectious intermediate (80.4%) or posterior uveitis (19.6%). The NEI VFQ-25 and the VFQ-UI demonstrated good internal consistency (Cronbach's alpha 0.87-0.94) and test-retest reliability (ICCs 0.58-0.88). Spearman's product-moment rank correlations between the NEI VFQ-25 and VFQ-UI scores and the SF-6D, EQ-5D, and BCVA ranged from small to moderate. There was a significant association between visual functioning and known groups of visual acuity (p<0.05). Clinical significance, using the anchor-based method (difference between visual acuity groups≥10-<15 letter better and no change), was 10.2 for change from baseline to week 26 for the NEI VFQ-25 composite score and 0.05 for the VFQ-UI. Using the distribution-based method, the clinical significance was 3.86 for the composite score and 0.04 for the VFQ-UI. The NEI VFQ-25 and the VFQ-UI are reliable and valid measures of vision-related functioning and preference-based status in patients with non-infectious intermediate and posterior uveitis.

Ocular tolerability and efficacy of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis: primary 6-month results of the SAVE Study

BackgroundThe purpose of this study is to evaluate the ocular tolerability and efficacy of sirolimus administered as subconjunctival or intravitreal injections in patients with non-infectious uveitis. Sirolimus as a Therapeutic Approach for Uveitis (SAVE) is a prospective, randomized, open-label, interventional study. Thirty patients were enrolled and randomized in 1:1 ratio to receive either intravitreal injections of 352 μg sirolimus or subconjunctival injections of 1,320 μg at days 0, 60, and 120, with primary endpoint at month 6.ResultsAt month 6, all subjects with active uveitis at baseline showed reduction in vitreous haze of one or more steps. Forty percent of subjects showed reduction of two steps or more of vitreous haze (four in each group), and 60% showed a reduction of one-step vitreous haze (seven in group 1 and five in group 2). Changes in the inflammatory indices were statistically significant (p < 0.05) in both study groups. Thirty percent of patients gained one or more lines of visual acuity, 20% lost one or more lines, and 50% maintained the same visual acuity. There were no statistically significant differences between the two study groups at month 6. No serious adverse events were found to be related to the study drug.ConclusionLocal administration of sirolimus, either intravitreally or subconjunctivally, appears to be safe and tolerable. No drug-related systemic adverse events or serious adverse events were noted. Sirolimus delivered as either an intravitreal or subconjunctival injection has demonstrated bioactivity as an immunomodulatory and corticosteroid-sparing agent in reducing vitreous haze and cells, improving visual acuity, and in decreasing the need for systemic corticosteroids.