Ocular features of the HLA-B27-positive seronegative spondyloarthropathies.

PURPOSE OF REVIEW: The seronegative spondyloarthropathies are a closely related group of inflammatory diseases that include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, inflammatory bowel disease and undifferentiated spondyloarthritis. This review focuses on the spectrum of ocular manifestations associated with these diseases and the current approaches in treating these ocular manifestations. It also highlights the role ophthalmologists can play in identifying and appropriately treating human leukocyte antigen B27 (HLA-B27) associated uveitis and the associated spondyloarthropathies in order to limit ocular and systemic morbidity. RECENT FINDINGS: Evolving treatment paradigms for the seronegative spondyloarthropathies should direct the choice in therapeutic agent for difficult to control associated uveitis. Biologic therapies, particularly tumor necrosis factor inhibitors, are playing an increasing role in the treatment. SUMMARY: Acute anterior uveitis is the most common ocular manifestation in HLA-B27 positive seronegative spondyloarthropathies. Suspicion for HLA-B27 associated uveitis should prompt a careful clinical history and rheumatologic referral if symptoms of an inflammatory arthropathy are present. Therapy is tailored based on severity of ocular and systemic manifestations with interventions from topical corticosteroids to immunomodulating agents available in treating these diseases.

Regional Variations in Orbicularis Oculi Histology.

PURPOSE: To investigate and compare the histologic compositions of the pretarsal, preseptal, and orbital orbicularis oculi muscle (OOM) using nonpreserved, fresh-frozen, human cadavers. METHODS: The OOM was exposed using sharp and blunt dissection. A metric ruler was used to measure and mark 0.5 cm × 1 cm samples from each portion of the right, superior OOM. Samples were excised, fixed in formalin, and completely embedded in paraffin. Five-micrometer-thick, hematoxylin- and eosin-stained sections were generated for each sample and analyzed by an anatomical pathologist. The relative percentages of the 4 main tissue types (skeletal muscle, fibrous tissue, adipose tissue, and neurovascular tissue) were quantified. RESULTS: Forty-two samples were obtained from 14 Caucasian cadavers. On average, the pretarsal samples were composed of 83.5% skeletal muscle, 0.0% adipose, 5.0% neurovascular, and 11.5% fibrous tissue. Average preseptal OOM was 46.5% skeletal muscle, 12.7% adipose, 9.2% neurovascular, and 31.5% fibrous tissue. The orbital OOM was, on average, 42.7% skeletal muscle, 32.7% adipose tissue, 6.9% neurovascular, and 17.7% fibrous tissue. CONCLUSIONS: The OOM represents a histologically heterogeneous structure.

Manifestations and Management of Inflammatory Eye Disease in Patients with Inflammatory Bowel Disease.

PURPOSE: To characterize the ocular inflammatory manifestations of inflammatory bowel disease (IBD) and examine the impact of ocular inflammation on IBD treatment. METHODS: A single-center retrospective chart review of patients with an IBD diagnosis and ophthalmology visit between January 2016 and January 2022 was conducted. Patients with a diagnosis of uveitis, scleritis, or peripheral ulcerative keratitis (PUK) confirmed by an optometrist or ophthalmologist were included. RESULTS: Charts of 1320 IBD patients were reviewed; 42 patients with uveitis, 2 patients with scleritis, and 2 patients with PUK were identified. Anterior uveitis was the most common form of uveitis (38/42, 90.5%), often in an episodic (31/38, 81.6%) and unilateral (19/38, 50.0%) pattern. Four patients (4/42, 9.5%) had posterior segment uveitis: two with panuveitis, one with intermediate uveitis, and one with posterior uveitis. Patients on systemic therapy for IBD did not routinely undergo changes to therapy following the development of ocular inflammation (27/36, 75.0%). Therapy alterations were more frequent with the development of posterior segment uveitis, scleritis, or PUK (4/6, 66.7%) compared with anterior uveitis (5/30, 16.7%). In 10 patients, uveitis onset preceded IBD diagnosis; in these patients, tumor necrosis factor (TNF) inhibitors were often used at the time of subsequent IBD diagnosis (5/10, 50.0%). CONCLUSIONS: Unilateral anterior uveitis was the most common form of ocular inflammation among patients with IBD. Development of uveitis did not routinely require modification of immunomodulatory therapies; however, therapy changes were more common with posterior segment uveitis, scleritis, and PUK.

Aspergillus Endophthalmitis Secondary to Infectious Scleritis: Utility of Diagnostic PCR.

PURPOSE: To describe a case of delayed-onset Aspergillus fumigatus endophthalmitis secondary to infectious fungal scleritis diagnosed with broad range polymerase chain reaction (PCR) from scleral nodular debridement and vitreous sampling during vitrectomy. METHODS: Retrospective case report with slit lamp photography, optical coherence tomography, and fundus photography. RESULTS: A 76-year-old man presented with right eye worsening vision and pain concerning for progressive nodular scleritis and endophthalmitis eight months following a reportedly innocuous tree branch injury. Following the injury, he underwent an MRI, surgical exploration, subconjunctival antibiotic administration, and culturing due to persistent foreign body sensation. Cultures were negative, and the patient was started on oral NSAIDs, oral prednisone, and periocular triamcinolone injections following negative/normal infectious and rheumatologic workup for scleritis. The patient was referred for worsened scleritis with development of endophthalmitis. He underwent lamellar sclerectomy, debridement, and culture of purulent material from scleral nodules in coordination with diagnostic vitrectomy, vitreous sampling, and subconjunctival and intravitreal antibiotic and antifungal treatment. Broad range PCR was positive for Aspergillus fumigatus and targeted antifungal treatment initiated. The eye did not regain visual function and was enucleated for progressive pain six months following diagnosis. CONCLUSION: Fungal scleritis and endophthalmitis results in significant morbidity. Diagnostic vitrectomy and broad range PCR can aid in prompt diagnosis and targeted treatment, and may be useful in refractory cases.

Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.

We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH (P < 10(-75)), ARMS2 (P < 10(-59)), C2/CFB (P < 10(-20)), C3 (P < 10(-9)), and CFI (P < 10(-6)). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 x 10(-11)), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci (LIPC, P = 1.3 x 10(-7); CETP, P = 7.4 x 10(-7)) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c-associated alleles near LPL (P = 3.0 x 10(-3)) and ABCA1 (P = 5.6 x 10(-4)). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.

Therapeutic Outcomes of Non-Infectious Scleritis Treated with Tumor Necrosis Factor-Alpha Inhibitors.

PURPOSE: We determine the efficacy of tumor necrosis factor-α (TNF) inhibitors in establishing scleritis quiescence. METHODS: We conducted a multicenter retrospective chart review of patients with non-infectious scleritis treated with a TNF inhibitor for at least 6 months. The primary endpoint was scleritis quiescence at 6 months. Secondary endpoints included scleritis quiescence at 12 months, TNF inhibitor effects on concurrent doses of systemic corticosteroids and visual acuity outcomes at 6 and 12 months. RESULTS: At 6 months, 82.2% (37/45) of subjects obtained scleritis quiescence with TNF inhibition. At 12 months, 76.2% (32/42) of subjects remained quiescent. Baseline daily corticosteroid use (21.5 ± 21.6 mg) decreased to 5.4 ± 8.3 mg by 6 months (p < 0.0001) and 2.8 ± 6.1 mg by 12 months (p < 0.001). There was no significant difference between the baseline and 6-month BCVA (p = 0.52). CONCLUSIONS: TNF inhibitors are an effective scleritis therapy with significant systemic corticosteroid sparing effect.

Risk Factors Associated with Unexpected Refractive Outcomes in Uveitic Cataract Surgery.

OBJECTIVE: Assess refractive outcomes following uveitic cataract surgery and identify factors associated with deviations from the target refractive goal. METHODS: A multicenter retrospective chart review was performed for 216 subjects with uveitis undergoing cataract surgery. Prediction error was calculated and tested for association with demographic and clinical characteristics using single variable and multiple regression analysis. RESULTS: 39.8% of eyes deviated from the intended refractive target by at least 0.5 diopters (D). The mean prediction error was 0.56 ± 0.67 D. Younger age (p = 0.042), preoperative inflammatory corneal findings (keratic precipitates and/or band keratopathy) (p = 0.0004), and poorer postoperative visual acuity (p = 0.0054) were associated with a deviation from the intended refractive target by at least 1 D. CONCLUSIONS: A higher percentage of eyes undergoing uveitic cataract surgery deviated from the intended refractive target when compared to reported refractive outcomes in normal subjects. Younger age, preoperative inflammatory corneal sequelae, and poorer postoperative visual acuity were associated with this outcome.

Characteristics and Outcomes of Patients with Scleritis in the IRIS® Registry (Intelligent Research in Sight) Database.

Purpose: To report patient characteristics and factors associated with poor visual acuity and abnormal intraocular pressure (IOP) in patients with scleritis in the American Academy of Ophthalmology's IRIS® Registry (Intelligent Research in Sight). Design: Retrospective cohort study. Participants: Patients in the IRIS Registry with at least 3 office visits associated with an International Classification of Diseases scleritis code from 2013 through 2019. Methods: We evaluated demographic and clinical characteristics in scleritis and scleritis subtype cohorts. We conducted Cox proportional hazards and multiple logistic regression analyses to assess associations with poor best-corrected visual acuity (BCVA), vision loss, and IOP abnormalities. Main Outcome Measures: Patient characteristics, BCVA of 0.6 logarithm of the minimum angle of resolution (logMAR) or more, BCVA worsened by more than 3 logMAR units 6 months after presentation, IOP of 30 mmHg or more, and IOP of 5 mmHg or less. Results: In this cohort of 111 314 patients with scleritis, the mean ± standard deviation age was 58.5 ± 16.6 years, 66% were women, and 30% had bilateral scleritis. Patients with scleromalacia perforans were older and more likely to have bilateral disease. Multiple logistic regression analysis identified factors with increased odds for poor presenting BCVA (older age, male sex, Black race, Hispanic ethnicity, smoking, and scleritis subtypes) and at least 3 lines of vision loss 6 months after initial scleritis diagnosis (older age, smoking, and anterior scleritis). Cox proportional hazards regression modeling of BCVA of 0.6 logMAR or more showed older age (adjusted hazard ratio [aHR] per 10-year unit, 1.11), Black race (aHR, 1.19), Hispanic ethnicity (aHR, 1.22), active smoking (aHR, 1.39), former smoking (aHR, 1.26), and certain scleritis subtypes increase the risk of poor visual acuity development (P < 0.001 for all). Older age, male sex, Black race, Hispanic ethnicity, smoking, and scleritis subtypes increased the odds of IOP abnormality. Conclusions: Older age, Black or Hispanic ancestry, smoking, and specific scleritis subtypes are risk factors for worse visual and IOP outcomes in patients with scleritis in the IRIS Registry. Closer follow-up may be appropriate for older, Black, or Hispanic patients with scleritis; smokers should receive smoking cessation assistance.

Syphilitic interstitial keratitis treated with topical tacrolimus.

PURPOSE: To report a case of syphilitic interstitial keratitis successfully managed with topical tacrolimus after the development of steroid-induced intraocular pressure elevation in a pediatric patient. OBSERVATIONS: A 4-year-old female with a history of congenital syphilis that was reportedly treated after birth presented with bilateral conjunctival redness, tearing, and photosensitivity. Initial ophthalmic examination revealed corneal vascularization with diffuse haze of the right eye and circumferential vascularization with stromal infiltrates of the left eye. She was diagnosed with bilateral syphilitic interstitial keratitis and initially managed with topical steroids but developed steroid-induced elevation of her intraocular pressure. She experienced several recurrences of keratitis as steroids were tapered. After a recurrence in her right eye, she was treated with topical tacrolimus. Since then, she has remained recurrence-free for almost three years with normal intraocular pressure. CONCLUSION AND IMPORTANCE: Tacrolimus represents a novel alternative for the treatment of syphilitic interstitial keratitis, which is particularly useful in patients that develop elevated intraocular pressures in response to long-term treatment with steroid eye drops.

Characterization and Management of Inflammatory Eye Disease in Patients with Hidradenitis Suppurativa.

Purpose: To assess the spectrum and treatment outcomes of inflammatory eye disease (IED) in subjects with hidradenitis suppurativa (HS).Methods: We conducted a single center retrospective chart review of 236 patients with HS seen for ophthalmic examination between 2013 and 2018.Results: Of 236 subjects with HS, 22 subjects (9.3%) were found to have IED. Seven of 22 subjects had more than one IED diagnosis. Anterior uveitis was the most common type of IED (40.9% of subjects with IED). Episcleritis, optic neuritis, keratitis, scleritis, intermediate and posterior uveitis, trochleitis, and dacryoadenitis were also observed. Of subjects with HS and IED, 59.1% did not have any other inflammatory or autoimmune disease that could explain the etiology of their IED. Eleven patients with IED were treated with systemic immunosuppression, with IED as the principal factor directing treatment in three patients.Conclusions: IED may be independently associated with HS and may benefit from systemic immunosuppression.

Uveitis reactivation following recombinant zoster vaccination.

PURPOSE: Describe three cases of uveitis reactivation following immunization with recombinant zoster vaccine (RZV). OBSERVATIONS: One patient developed reactivation of previously controlled multifocal choroiditis within one week of receiving RZV, requiring treatment with systemic corticosteroids. Two patients with previously controlled anterior uveitis developed new anterior segment inflammation after RZV; both were treated with topical corticosteroids and systemic antiviral therapy. CONCLUSION AND IMPORTANCE: Uveitis recurrence is an infrequent but serious potential ocular side effect of recombinant zoster vaccination.

Treatment of Refractory Cystoid Macular Edema with Pegylated Interferon Alfa-2A: A Retrospective Chart Review.

Purpose: To determine the efficacy of pegylated interferon alfa-2A in the treatment of refractory inflammatory cystoid macular edema (CME)Methods: Retrospective chart reviewResults: Treatment with pegylated interferon alfa-2A led to an improvement in CME in all eyes of seven included patients, with a mean decrease in CMT from 478 µm to 310 µm (p < .05). The vision in one patient did not improve due to preexisting retinal atrophy. All other eyes showed improvement in vision, with a mean improvement in best LogMAR visual acuity from +0.59 to +0.28 (p < .05). The treatment effect was sustained with low-dose treatment every 2 weeks or less in the majority of patients. Two patients who stopped interferon treatment given flu-like symptoms and intolerable rash, respectively, showed rapid recurrence of CME.Conclusions: Weekly administration of pegylated interferon alfa-2A is an effective treatment for refractory inflammatory CME, though side effects may limit tolerability in some patients.

Thrombocytopenia and clear corneal incision cataract surgery.

PURPOSE: To investigate complications and outcomes of clear corneal incision cataract surgery in patients with thrombocytopenia. SETTING: 1 veterans hospital and 2 academic medical centers. DESIGN: Multicenter retrospective chart review. METHODS: All eyes of thrombocytopenic patients that underwent clear corneal incision cataract surgery with a platelet count of 100 × 103/µL or less measured within 30 days prior to surgery were included. Subject demographics, intraoperative complications, use of pupillary expansion devices, use of local anesthetic injections, and change in corrected distance visual acuity were recorded. RESULTS: 3 sites recorded 40 113 clear corneal incision cataract surgeries, of which 196 eyes (0.49%) of 150 thrombocytopenic patients were recorded. The mean platelet count in the study subjects was 73.0 ± 20.5 × 103/µL. Two cases of intraoperative iris hemorrhage that were readily and controlled occurred in conjunction with pupillary expansion. There were no bleeding complications associated with retrobulbar, peribulbar, or sub-Tenon anesthetic injections. There was a statistically significant improvement (P < .0001) in visual acuity post-operatively. CONCLUSIONS: Clear corneal incision cataract surgery with pupillary expansion devices and local anesthetic injections can be safely performed in patients with thrombocytopenia.

Age-related retinal degeneration (arrd2) in a novel mouse model due to a nonsense mutation in the Mdm1 gene.

We observed that a naturally occurring mouse strain developed age-related retinal degeneration (arrd2). These mice had normal fundi, electroretinograms (ERGs) and retinal histology at 6 months of age; vessel attenuation, RPE atrophy and pigmentary abnormalities at 14 months, which progressed to complete loss of photoreceptors and extinguished ERG by 22 months. Genetic analysis revealed that the retinal degeneration in arrd2 segregates in an autosomal recessive manner and the disease gene localizes to mouse chromosome 10. A positional candidate cloning approach detected a nonsense mutation in the mouse double minute-1 gene (Mdm1), which results in the truncation of the putative protein from 718 amino acids to 398. We have identified a novel transcript of the Mdm1 gene, which is the predominant transcript in the retina. The Mdm1 transcript is localized to the nuclear layers of neural retina. Expression of Mdm1 in the retina increases steadily from post-natal day 30 to 1 year, and a high level of Mdm1 are subsequently maintained. The Mdm1 transcript was found to be significantly depleted in the retina of arrd2 mice and the transcript was observed to degrade by nonsense-mediated decay. These results indicate that the depletion of the Mdm1 transcript may underlie the mechanism leading to late-onset progressive retinal degeneration in arrd2 mice. Analysis of a cohort of patients with age-related macular degeneration (AMD) wherein the susceptibility locus maps to chromosome 12q, a region bearing the human ortholog to MDM1, did not reveal association between human MDM1 and AMD.

Pathological Findings of Synchysis Scintillans Secondary to Familial Exudative Vitreoretinopathy With Chronic Exudative Retinal Detachment.

Purpose: We describe a unique case of synchysis scintillans in a 23-year-old woman with a history of chronic exudative retinal detachment in the setting of familial exudative vitreoretinopathy. Methods: Fundus and slit-lamp photographs were obtained at presentation, and pathological studies were performed on the enucleated specimen to confirm the diagnosis. Results: Synchysis scintillans is a degenerative condition of cholesterol deposition that affects severely damaged eyes, often as a result of chronic vitreous hemorrhage or retinal detachment. In this case, synchysis scintillans presented as crystals in the anterior chamber in the setting of a chronic retinal detachment. After enucleation, there were noted to be cholesterol slits on pathological correlation, confirming the diagnosis. Conclusions: This case demonstrates the importance of clinical pathological correlation in the diagnosis of synchysis scintillans migrating into the anterior chamber.

Association of Fundus Autofluorescence Findings and Outer Retinal Lesions on Optical Coherence Tomography With Visual Acuity in Birdshot Chorioretinopathy.

PURPOSE: This article investigates the optical coherence tomography (OCT) and fundus autofluorescence imaging findings in birdshot chorioretinopathy (BSCR) and their association with visual acuity (VA). METHODS: In a retrospective, cross-sectional study, we evaluated OCT images for changes in retinal structure including cystoid macular edema (CME), epiretinal membrane, and outer retinal lesions. We assessed autofluorescence images for hypoautofluorescent and hyperautofluorescent changes and noted the distribution of the lesions. Demographic data and VA at the time of imaging were also collected. Associations between OCT and autofluorescence findings and logarithm of the minimum angle of resolution VA were tested using linear regression. RESULTS: We conducted a chart review of 80 eyes from 40 patients with BSCR. Outer retinal lesions were found on OCT in 28 of 80 eyes (35%) and disruption of the outer segment ellipsoid zone (EZ) occurred in 23 eyes (28.7%). Macular hypoautofluorescent lesions were more common than hyperautofluorescent lesions, present in 58.8% and 13% of eyes, respectively. The presence of outer retinal lesions on OCT was significantly associated with reduced VA (P = .006) as was EZ disruption (P = .003). These associations remained significant after accounting for the presence of macular edema. There was a trend toward association of macular hypoautofluorescent lesions with decreased vision, although it was not statistically significant (P = .17). CONCLUSIONS: The association of outer retinal lesions with decreased VA suggests a mechanism of central vision loss that is distinct from CME and may provide an additional objective finding to monitor disease activity in BSCR patients.

Retinal vasculitis associated with CREST syndrome.

PURPOSE: To report two cases of retinal vasculitis associated with CREST syndrome, a novel ocular finding. OBSERVATIONS: We report two cases of patients with CREST syndrome with ocular inflammatory disease. Patient 1 presented with a right unilateral panuveitis with extensive retinal vasculitis and evidence of prior uveitis in the contralateral eye. Patient 2 presented with a left branch retinal artery occlusion and bilateral retinal vasculitis. Both patients underwent treatment with prednisone and mycophenolate motefil. CONCLUSIONS AND IMPORTANCE: Retinal vasculitis has not been previously reported in CREST syndrome. Prompt therapy with immunomodulatory therapy can potentially minimize ocular morbidity.

Visual acuity recovery following traumatic hyphema in a pediatric population.

PURPOSE: To determine the rate of visual recovery following hyphema caused by traumatic blunt force injury in children. METHODS: The medical records of patients evaluated between July 2008 and July 2014 were reviewed retrospectively. Primary outcome measures included presenting and follow-up visual acuities. RESULTS: At total of 56 eyes of 55 children (<18 years of age) were diagnosed with hyphema following blunt force nonpenetrating injury. The average patient age was 10.3 ± 3.2 years. The majority of subjects were male (78%). Presenting visual acuities ranged from logMAR 0.0 (Snellen equivalent, 20/20) to light perception. Rebleeding occurred in 4 subjects (7.1%). Visual acuity demonstrated improvement over the first 28 days following injury, with 59% achieving visual acuity of logMAR 0.0 (Snellen equivalent, 20/20) and 82% recovering vision to logMAR 0.2 (Snellen equivalent 20/30) by day 28. All but 1 patient (43 of 44 eyes, 98%) had a best-corrected visual acuity of better than or equal to logMAR 0.2 at their last recorded follow-up. CONCLUSIONS: There is good potential for visual recovery following uncomplicated traumatic hyphema in children. In our patient cohort, the majority of patients had significant improvement in visual acuity within the first 28 days; in some children visual acuity continued to improve beyond the first month.

Correction: A 32 kb Critical Region Excluding Y402H in CFH Mediates Risk for Age-Related Macular Degeneration.

[This corrects the article DOI: 10.1371/journal.pone.0025598.].