Bilateral Acute Iris Transillumination Following Systemic Moxifloxacin for Respiratory Illness: Report of Two Cases and Review of the Literature

Purpose: To describe two cases of bilateral acute iris transillumination following systemic administration of moxifloxacin and review the literature.

Methods: Review of clinical records, and review of the literature using the PubMed database.

Results: A 75 year-old man and 33 year-old woman presented with bilateral conjunctival injection, photophobia, and atonic, distorted pupils. The symptoms began acutely following a respiratory illness, for which both were treated with moxifloxacin. Both patients demonstrated profound iris transillumination, sectoral posterior bowing of the iris, corneal endothelial pigment dusting, and trabecular meshwork hyperpigmentation. One patient had a cotton-wool spot. A literature review identified 59 previous reports in 5 publications, including 17 patients with no antecedent fluoroquinolone use.

Conclusions: Increased awareness of this recently described clinical entity should lead to a decrease in unnecessary diagnostic evaluations. It is currently unclear whether this disease represents an adverse effect of fluoroquinolone use or a sequela of a systemic illness.     

Anterior Segment Applications of Optical Coherence Tomography Angiography

ABSTRACT

Purpose: To review the current literature regarding optical coherence tomography angiography (OCT-A) applications in the anterior segment.

Methods: A literature search was performed for terms including OCT-Angiography, anterior segment, cornea, conjunctiva, iris, applications and use in ophthalmology.

Results: Fifteen studies were identified, 14 in human subjects. Studies with OCT-A of the conjunctiva, episclera, cornea, and iris were identified, some with normal eyes imaged and others with various pathologies. Most of these studies imaged corneal neovascularization. Three studies described protocols used for image acquisition, one of which was referenced by two later papers.

Conclusions: OCT-A is a noninvasive technology with recent applications in the anterior segment. Several pilot studies have been performed on various anterior segment structures and disease states however standardization of image acquisition techniques is still needed. Future imaging could allow noninvasive and serial monitoring of pathology as well as recurrence after therapeutic intervention.     

Novel use of non-echo-planar diffusion weighted MRI in monitoring disease activity and treatment response in active Grave’s orbitopathy: An initial observational cohort study

Aim: To examine the novel use of non-echo-planar diffusion weighted MRI (DWI) in depicting activity and treatment response in active Grave’s orbitopathy (GO) by assessing, with inter-observer agreement, for a correlation between its apparent diffusion coefficients (ADCs) and conventional Short tau Inversion Recovery (STIR) MRI signal-intensity ratios (SIRs).

Method and Materials: A total of 23 actively inflamed muscles and 30 muscle response episodes were analysed in patients with active GO who underwent medical treatment. The MRI orbit scans included STIR sequences and non-echo-planar DWI were evaluated. Two observers independently assessed the images qualitatively for the presence of activity in the extraocular muscles (EOMs) and recorded the STIR signal-intensity (SI), SIR (SI ratio of EOM/temporalis muscle), and ADC values of any actively inflamed muscle on the pre-treatment scans and their corresponding values on the subsequent post-treatment scans. Inter-observer agreement was examined.

Results: There was a significant positive correlation (0.57, p < 0.001) between ADC and both SIR and STIR SI of the actively inflamed EOM. There was also a significant positive correlation (0.75, p < 0.001) between SIR and ADC values depicting change in muscle activity associated with treatment response. There was good inter-observer agreement.

Conclusion: Our preliminary results indicate that quantitative evaluation with non-echo-planar DWI ADC values correlates well with conventional STIR SIR in detecting active GO and monitoring its treatment response, with good inter-observer agreement.     

Agreement in Measurement of Optic Cup-to-Disc Ratio with Stereo Biomicroscope Funduscopy and Digital Image Analysis: Results from the Nigeria National Blindness and Visual Impairment Survey

Purpose: To determine agreement in estimations of vertical cup-to-disc ratio (VCDR) between clinical stereo-biomicroscopic funduscopy and digital fundus image analysis.

Methods: Systematic sampling of 1-in-7 from a sample of 13,591 participants aged ≥40 years gave a subsample who were examined in detail. VCDR was estimated clinically by 60 diopter aspheric lens biomicroscopic funduscopy (c-VCDR) and by digital fundus images (i-VCDR) graded at the Moorfields Eye Hospital Reading Centre. Spearman’s correlation coefficient, paired t-test and the Bland-Altman method to assess limits of agreement (LOA) between the two methods were applied.

Results: Of 1759 participants in the subsample, 848 participants (48%) with normal frequency doubling technology (FDT) visual fields and data for i-VCDR and c-VCDR in both eyes (n = 1696 eyes) were included in the analysis. By absolute difference of VCDR values for each eye between the two methods, 1585 eyes (94%) differed by ≤0.2. Mean i-VCDR was 0.381 (standard deviation, SD 0.156), and mean c-VCDR 0.321 (SD 0.145). i-VCDRs were significantly larger by a mean difference of 0.061 (SD 0.121; 95% confidence interval, CI, 0.055–0.066; p < 0.001). The 95% LOA assessed by the Bland-Altman method were lower limit ?0.182 (95% CI ?0.192 to ?0.172) and upper limit 0.303 (95% CI 0.293–0.313). The 95% LOA intervals narrowed with higher VCDR.

Conclusion: Digital image analysis and clinical assessment are two distinct methods to measure VCDR; with larger i-VCDRs in this survey. Applying i-VCDR cut-off values to c-VCDR measurements in the Nigeria Blindness Survey might have underestimated glaucoma prevalence. It is recommended that all participants in glaucoma surveys have VCDR by digital image measurement.     

A Bayesian Analysis of a Randomized Clinical Trial Comparing Antimetabolite Therapies for Non-Infectious Uveitis

Purpose: To conduct a Bayesian analysis of a randomized clinical trial (RCT) for non-infectious uveitis using expert opinion as a subjective prior belief.

Methods: A RCT was conducted to determine which antimetabolite, methotrexate or mycophenolate mofetil, is more effective as an initial corticosteroid-sparing agent for the treatment of intermediate, posterior, and pan-uveitis. Before the release of trial results, expert opinion on the relative effectiveness of these two medications was collected via online survey. Members of the American Uveitis Society executive committee were invited to provide an estimate for the relative decrease in efficacy with a 95% credible interval (CrI). A prior probability distribution was created from experts’ estimates. A Bayesian analysis was performed using the constructed expert prior probability distribution and the trial’s primary outcome.

Results: A total of 11 of the 12 invited uveitis specialists provided estimates. Eight of 11 experts (73%) believed mycophenolate mofetil is more effective. The group prior belief was that the odds of treatment success for patients taking mycophenolate mofetil were 1.4-fold the odds of those taking methotrexate (95% CrI 0.03–45.0). The odds of treatment success with mycophenolate mofetil compared to methotrexate was 0.4 from the RCT (95% confidence interval 0.1–1.2) and 0.7 (95% CrI 0.2–1.7) from the Bayesian analysis.

Conclusions: A Bayesian analysis combining expert belief with the trial’s result did not indicate preference for one drug. However, the wide credible interval leaves open the possibility of a substantial treatment effect. This suggests clinical equipoise necessary to allow a larger, more definitive RCT.     

Changes in Iris Stiffness and Permeability in Primary Angle Closure Glaucoma

PurposeTo evaluate the biomechanical properties of the iris by evaluating iris movement during pupil constriction and to compare such properties between healthy and primary angle-closure glaucoma (PACG) subjects.MethodsA total of 140 subjects were recruited for this study. In a dark room, the anterior segments of one eye per subject were scanned using anterior segment optical coherence tomography imaging during induced pupil constriction with an external white light source of 1700 lux. Using a custom segmentation code, we automatically isolated the iris segments from the AS-OCT images, which were then discretized and transformed into a three-dimensional point cloud. For each iris, a finite element (FE) mesh was constructed from the point cloud, and an inverse FE simulation was performed to match the clinically observed iris constriction in the AS-OCT images. Through this optimization process, we were able to identify the elastic modulus and permeability of each iris.ResultsFor all 140 subjects (95 healthy and 45 PACG of Indian/Chinese ethnicity; age 60.2 ± 8.7 for PACG subjects and 57.7 ± 10.1 for healthy subjects), the simulated deformation pattern of the iris during pupil constriction matched well with OCT images. We found that the iris stiffness was higher in PACG than in healthy controls (24.5 ± 8.4 kPa vs. 17.1 ± 6.6 kPa with 40 kPa of active stress specified in the sphincter region; P < 0.001), whereas iris permeability was lower (0.41 ± 0.2 mm²/kPa s vs. 0.55 ± 0.2 mm²/kPa s; p = 0.142).ConclusionsThis study suggests that the biomechanical properties of the iris in PACG are different from those in healthy controls. An improved understanding of the biomechanical behavior of the iris may have implications for the understanding and management of angle-closure glaucoma.     

Clinical outcome and endothelial loss following prepupillary and retropupillary implantation of iris claw intraocular lenses

Purpose

Iris claw intraocular lenses (IOLs) were successfully used for the management of aphakia in patients that lack capsular support. The aim of this study was to compare the clinical outcome of prepupillary and retropupillary implantation of these IOLs.

Methods

The files of the 26 patients that had an iris claw IOL implantation between 2010 and 2020 were retrospectively reviewed. Detailed ophthalmological examination findings including corrected distance visual acuity (CDVA), intraocular pressure, endothelial cell counts, slit lamp and dilated fundus examination findings were specifically tabulated. Intraoperative and postoperative complications were also specifically recorded.

Results

There were 18 patients in the prepupillary implantation group and eight patients in the retropupillary implantation group. Age and gender distribution were similar between the groups. CDVA significantly increased in prepupillary and retropupillary implantation groups (p?=?0.001 and p?=?0.012, respectively). Median endothelial cell loss was 6.7% in prepupillary group and 7.2% in retropupillary group. The only intraoperative complication was iridodialysis (n?=?1). Postoperative complications included retinal detachment (n?=?1), cystoid macular edema (n?=?2) and IOL tilt (n?=?1). All of these complications occurred in the prepupillary implantation group.

Conclusion

Prepupillary and retropupillary implantation of iris claw IOLs resulted with similar visual gain and endothelial loss rates in a follow-up time of 6 months. There was an insignificant trend toward a reduced complication rate following retropupillary implantation.

     

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

Abstract

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.     

Repair of Iridodialysis Using 8-0 Polypropylene

Abstract

Purpose: Investigate the effectiveness of repair of iridodialysis with 8-0 polypropylene. Methods: We present four cases of traumatic iridodialysis that were repaired by 8-0 polypropylene suture. Results: Better iris reposition and stability were achieved with 8-0 polypropylene suture despite wide degree traumatic iridodialysis in all patients. Conclusion: In this study, we used 8-0 polypropylene suture, which is thicker, cheaper, and more durable than 10-0 sutures. We suggest that usage of 8-0 polypropylene sutures may provide better iris repositioning.     

Recovery of the Ellipsoid and Interdigitation Zones in Acute Behcet’s Uveitis after Therapy

ABSTRACT

Purpose: To report acute photoreceptor layers loss in Behcet’s disease and its anatomical recovery after treatment with systemic steroids, mycophenolate mofetil, and adalimumab.

Methods: Case report.

Results: A 16-year-old male who presented with an acute attack of Behcet’s panuveitis along with loss of the ellipsoid zone (EZ) and interdigitation zone (IZ) on optical coherence tomography (OCT). Treatment resulted in complete recovery of photoreceptors and improvement in vision.

Conclusion: Acute photoreceptor layers loss could be a manifestation of Behcet’s uveitis and anatomical recovery may be achieved with aggressive and timely treatment.     

Isolated foveal hypoplasia: report of a new case and detailed genetic investigation

To carry out an ophthalmological and detailed genetic investigation on a 7-year-old boy with isolated foveal hypoplasia. A full ophthalmological examination and optical coherence tomography (OCT) was performed. We also performed a full genome screen for chromosomal abnormalities, and searched for mutations in two genes (GPR143 and OCA2) known to be associated with ocular albinism and PAX6 gene known to be associated with aniridia. His eye examination was normal with no iris transillumination. A fundus examination, however, showed classic signs of foveal hypoplasia. A molecular genetic investigation showed no mutation(s) in all genes screened and no chromosomal deletion(s) and/or duplication(s) were detected. We report a case of isolated foveal hypoplasia where the underlying genetic cause could not be established. We could not rule out other genetic or epigenetic factors contributing to the pathogenesis of isolated foveal hypoplasia.     

Heterochromia pardus: implications of the spotted pale iris

A pale iris is a well-recognized feature of congenital Horner's syndrome. We studied a 42-year-old man who had right ptosis, miosis and a paler iris since early childhood. Not only was there diffuse hypochromic, but 25 /ij'/>erchromic pigmented spots were superimposed on the affected iris. Pharmacological testing confirmed that the iris was denervated by a postganglionic noradrenergic lesion but that some sympathetic input to the iris was still present. Clinical and radiographic studies showed an absent right internal carotid artery.

Mechanisms are reviewed by which the sympathetic nervous system influences pigmentation. Perinatal damage to neurons of the superior cervical ganglion with subsequent partial reinnervation may account for some features of our patient's distinctive spots. A term 'heterochromia pardus' appears to characterize both the spotting and the pallor of the iris.     

Bilateral Iris Depigmentation and Ocular Hypotony as End-Stage Manifestations of Untreated Vogt–Koyanagi–Harada Disease

Purpose: To describe severe bilateral iris depigmentation and persistent ocular hypotony as end-stage manifestations of untreated Vogt–Koyanagi–Harada disease.

Methods: We present the clinical findings and diagnostic studies performed for three patients with bilateral iris depigmentation.

Results: Vogt–Koyanagi–Harada disease in late recurrent stage was diagnosed in three patients with bilateral severe iris depigmentation and persistent ocular hypotony.

Conclusions: Early diagnosis and treatment of inflammation are crucial factors in the clinical outcome of Vogt–Koyanagi–Harada disease. When left undiagnosed and untreated from early stages, severe iris depigmentation and ocular hypotony, uncommon manifestations of this disease, can develop.     

New method to analyze sagittal images of upper eyelid obtained by anterior segment optical coherence tomography

Purpose: To report a new method to analyze sagittal images of the upper eyelid by anterior segment optical coherence tomography (AS-OCT).

Methods: Ninety subjects equally divided into young (20–39 years), middle age (40–59 years), and elderly (60–79 years) group were studied. A sagittal image of the upper eyelid was obtained by AS-OCT (CASIA2, Tomey, Japan) and the following parameters were determined: upper eyelid thickness (UET), the distance between two parallel lines tangential to the apexes of the cornea and the upper eyelid; the upper eyelid angle (UEA) was the angle formed by a line running tangential to the apex of the cornea and a line passing from the apex of the cornea to the apex of the upper eyelid; and the cross-sectional area (CSA), the area from the edge of the eyelid to a point 6 mm above the corneal apex. All parameters were compared among groups and correlation analyses were studied between age and eyelid parameters.

Results: The UET was 2.09 ± 0.58 mm, 2.63 ± 1.04 mm and 2.83 ± 0.83 mm in the young, middle age and elderly group, respectively. The difference between the young and the elderly group was significant (P = 0.014). The elderly group had a significantly larger UEA than that of young group (P = 0.022). The elderly group also had significantly larger CSA than the other two groups (all P < 0.01). The age was significantly correlated with all eyelid parameters.

Conclusions: AS-OCT can be used as a non-invasive and quantitative method of evaluating sagittal images of the upper eyelid.     

Fluocinolone Acetonide Intravitreal Implants in Vogt-Koyanagi-Harada Disease

Purpose: To describe the use of fluocinolone acetonide implants (Retisert) in Vogt-Koyanagi-Harada disease (VKH).

Design: Interventional case series.

Methods: Retrospective review of medical records.

Results: Two patients with VKH requiring high-dose systemic corticosteroid therapy to control their inflammation and bilateral serous retinal detachments received bilateral fluocinolone acetonide implants. Upon tapering of systemic corticosteroids, one patient had recurrent serous retinal detachments and the other patient’s anterior chamber and vitreous inflammation returned.

Conclusions: The authors’ experience with fluocinolone acetonide implants in VKH has been mixed with an inability to fully taper off of systemic corticosteroids.     

Statistical analyses of Endogenous Uveitis Patients (2007–2009) in central Tokyo area and Comparison with Previous Studies (1963–2006)

Abstract

Purpose: To investigate the frequencies of the diseases in the new patients with uveitis during 2007–2009 and compare them with previously-reported data from the University of Tokyo Hospital.

Methods: We retrospectively analyzed the clinical records of patients who visited the outpatient clinic from January 2007 to December 2009, and compared them with those of 1963–2006.

Results: During 2007–2009, 468 new patients visited our hospital. Definite diagnoses were made in 63.0%. Frequent diagnoses include sarcoidosis (9.4%), Vogt-Koyanagi-Harada (VKH) disease (7.9%), herpetic iritis (6.0%), Behçet’s disease (5.6%), Posner-Schlossman syndrome (4.3%), HLA-B27-associated uveitis (3.0%), and intraocular malignant lymphoma (2.8%). Compared with our former findings, the ratios of sarcoidosis, herpetic iritis, CMV retinitis, Fuch’s heterochromic iridocyclitis, acute retinal necrosis and intraocular lymphoma increased, while that of Behçet’s disease decreased.

Conclusions: Top three uveitis during 2007–2009 were sarcoidosis, VKH disease, herpetic iritis. Reduced frequency of Behçet’s disease was one of the most prominent characteristics.     

Pupil Dilation May Affect Retinal Vessel Caliber Measures

Purpose: To assess the effect of pupil dilation on measures of retinal vessel caliber.

Design: Observational study with self-comparisons

Methods: Retinal photographs were taken for both eyes of 25 subjects before and after pupil dilation. Three photographic graders, masked to pupil dilation status, measured the same set of images using a computer-assisted, semi-automatic method. We compared means (standard deviations) of retinal arteriolar caliber equivalent (CRAE) and retinal venular caliber equivalent (CRVE) of the same eyes between pre- and post-dilation images. We assessed concordance correlation coefficients (CC), Bland Altman limits-of-agreements, and used linear mixed models to assess CRAE and CRVE measures associated with pupil dilation (influencing image quality), graders (observers) and right-left eye variation.

Results: We found high CCs for CRAE (0.82-0.94) and CRVE (0.87-0.94) between pre- and post-dilation images of the same eyes across the graders. Bland Altman plots showed that mean differences ranged from 0.55-3.42μm for CRAE and 1.56-2.29μm for CRVE. After adjusting for right-left eye random variation, a significant fixed effect of dilation was evident in mean CRAE in two of the three graders. There was no significant fixed effect of dilation in mean CRVE across all graders. In models including data of both eyes’ measures from pre- and post-dilation images by three graders, the fixed effect for dilation status contributed significantly to CRAE and CRVE variances whereas random effects for graders and dilation status contributed minimally.

Conclusions: Contrary to our hypothesis, we found a systematic effect of pupil dilation on retinal vessel caliber measures.     

A novel missense mutation in BEST1 associated with an autosomal-dominant vitreoretinochoroidopathy (ADVIRC) phenotype

ABSTRACT

Background: To report a 68-year-old female with an autosomal-dominant vitreoretinochoroidopathy (ADVIRC) phenotype associated with a subretinal hemorrhage (SRH) and novel BEST1 pathogenic variation p.Met571Thr.

Materials and Methods: The patient was assessed by fundus photography, fluorescence and indocyanine green angiography, spectral-domain optical coherence tomography, photopic and scotopic electroretinogram (ERG), and electrooculogram (EOG). Whole-exome and Sanger sequencing of the patient’s and selected family members’ DNA was performed. Ophthalmoscopic examinations were also performed on six patient’s relatives.

Results: The patient presented moderate vitreous and SRH in the left eye. A distinct, annular hyperpigmented band was present in both eyes. Vitrectomy improved visual acuity, and the SRH gradually regressed without recurrence. Preserved macular function was shown by optical coherence tomography (OCT). Genetic analysis identified a novel heterozygous mutation, resulting in p.Met571Thr in BEST1. No mutations were observed in a panel of other eye disease genes, suggesting that this pathogenic variation in BEST1 is associated with an ADVIRC phenotype. No other evaluated family member had the variant or the fundus findings.

Conclusions: We present a patient with a novel p.Met571Thr pathogenic variation associated with an ADVIRC phenotype. SRH is a unique finding in ADVIRC patients and may correspond to peripheral exudative hemorrhagic chorioretinopathy. The BEST1 pathogenic variation p.Met571Thr might be the likely cause of ADVIRC in this patient. However, further study is necessary to determine whether this mutation is causative.     

Comparison of anterior chamber angle parameters and iris structure of juvenile open-angle glaucoma and pigmentary glaucoma

Purpose:To compare the quantitative measurements of the anterior chamber angle (ACA) and iris parameters in patients with juvenile open-angle glaucoma (JOAG), pigmentary glaucoma (PG), and healthy controls using anterior segment optical coherence tomography (AS-OCT).Methods:This was a retrospective, cross-sectional study of 25 eyes with JOAG, 25 eyes with PG, and 25 control eyes. Anterior chamber depth, angle-opening distance 500 and 750, trabecular–iris space 500 and 750, scleral spur angle, iris thickness (IT, measured at the thickest part), and iris bowing were obtained using AS-OCT (Visante” OCT 3.0 Model 1000, Carl Zeiss Meditec, Inc).Results:The quantitative ACA parameters were found to be significantly higher in JOAG and PG patients compared to healthy controls (P < 0.001); there was no significant difference between the eyes with JOAG and PG (P > 0.05). In eyes with JOAG and PG, there was significantly backward bowing of the iris in temporal and nasal angles compared to control subjects (P < 0.001). Median iris bowing was not significantly different between the patients with JOAG and PG (P > 0.05). The temporal and nasal angle iris thickness were significantly thinner in eyes with JOAG than the eyes with PG (P < 0.001) and age-matched control subjects (P < 0.001). The median IT did not differ between the patients with PG and control subjects (P > 0.05). In patients with JOAG, the intraocular pressure (IOP) was inversely correlated with IT (r = -0.43, P < 0.05).Conclusion:AS-OCT provided quantitative data on the ACA and iris parameters in JOAG and PG. The evaluation of the ACA and iris structures using AS-OCT revealed higher ACA measurements and posterior bowing of the iris in patients with JOAG and PG. Furthermore, the patients with JOAG were found to have thinner IT than the ones with PG and healthy controls.