Vitamin A deficiency retinopathy in the setting of celiac disease and liver fibrosis.

PURPOSE: Vitamin A is a lipid-soluble compound that is critical in maintaining phototransduction. Ocular manifestations of hypovitaminosis A may present with anterior segment signs of xeropthalmia, with advanced cases also causing classic retinal and electrophysiologic changes of vitamin A deficiency retinopathy. We present a case of vitamin A deficiency retinopathy, with corresponding retinal imaging and electrophysiology, in an adult patient with celiac disease and liver fibrosis. METHODS: A single case report was conducted in Toronto, Canada. RESULTS: A 77-year-old male with known celiac disease and liver fibrosis presented progressively worsening vision noticed primarily when driving. Vision was 20/50 OD and 20/200 OS. Bitot spots were noted on anterior segment examination. Fundus photography demonstrated bilateral peripheral macular hypopigmentation and far-peripheral granular retinal hypopigmentation with focal yellow dots and hyper-pigmented deposits. Optical coherence tomography (OCT) imaging demonstrated indistinct outer retinal banding with mild outer nuclear layer thinning, focal hyper-reflective deposits, and a thin choroid bilaterally. Full-field electroretinography (ERG) testing demonstrated reduced rod-isolated and combined rod-cone response amplitudes, and multifocal ERG testing demonstrated blunted individual responses throughout the field. The patient was treated with pulse vitamin A therapy. After 6 months of therapy, ERG responses were back within reference range, and the outer retinal changes reversed; visual acuity improved to 20/30 OD and 20/40 OS. CONCLUSION: This case represents the classic findings of vitamin A deficiency retinopathy on fundus examination and electrophysiologic testing secondary to gastrointestinal pathology. Prompt treatment of high dose vitamin A supplementation led to improvement of full-field and multifocal ERG results, as well as reconstitution of outer retinal architecture.

Wide-field true-colour imaging and clinical characterization of a novel GRK1 mutation in Oguchi disease.

PURPOSE: The available literature regarding Oguchi disease is limited, with around 50 cases described to date. Caused by mutations to either the SAG gene coding for arrestin (Hayashi et al. in Ophthalmic Res 46:175-180, 2011) or the GRK1 gene coding for rhodopsin kinase (Yamamoto et al. in Nat Genet 15:175-178. https://doi.org/10.1038/ng0297-175 , 1997), Oguchi disease is an autosomal recessive condition with a good visual prognosis. The clinical diagnosis of the condition is based on the presence of night blindness (nyctalopia), as well as fundoscopic observation of the Mizuo-Nakamura phenomenon. The Mizuo-Nakamura phenomenon refers to a fundus discolouration described as a golden-brown colour with a yellow-grey metallic sheen most prominent in the peripheral retina; after prolonged dark adaptation, the fundus appears normal. The prevalence of Oguchi disease is highest in Japan, particularly with SAG mutations (Nakazawa et al. in Retina 17:17-22, 1997), although patients from Europe, Pakistan and India have also been described. Formal diagnosis requires genetic testing. METHODS: Wide-field fundus images were obtained in both dark-adapted and light-adapted retina. Optical coherence tomography and dark-adapted electroretinography responses were used to further characterize the clinical phenotype. RESULTS: Existing descriptions of Oguchi disease have been limited by available technology. The flashes required for 45°-montage photographs in a dark-adapted eye quickly cause light adaptation. Recent advances in technology enable the capture of larger retinal areas in a single image. Wide-field 133° images were obtained of the native and dark-adapted fundus in natural colour. To our knowledge, these represent the first reported single-wide-field images of Oguchi disease, showing the characteristic Mizuo-Nakamura phenomenon in true colour. Genetic testing revealed a novel homozygous mutation in GRK1. CONCLUSIONS: Here, we demonstrate how characterizing this condition with single-shot true-colour wide-field imaging has distinct advantages over scanning laser technology, which applies artificial colouration, or stitched true-colour images. Images captured with wide-field systems create a much better representation of the native and dark-adapted fundus than can be observed by the ophthalmologist using direct fundoscopy and are essential in the clinical characterization of new mutations.

University of Toronto's redesigned ophthalmology curriculum and eye dissection lab.

OBJECTIVE: To present a multifaceted approach to ophthalmology undergraduate medical education and to assess the efficacy of an eye dissection laboratory in enhancing medical student learning. DESIGN: Curriculum review, validation, and student feedback evaluations. PARTICIPANTS: Year 2 medical students enrolled in the University of Toronto's Doctor of Medicine Program. METHODS: Student feedback evaluations were compiled from the University of Toronto undergraduate medical education student surveys before 2012-2016 and following introduction of the redesigned foundations ophthalmology curriculum at the University of Toronto (2017-2018). Students who participated in the Eye Dissection Lab as part of the newly designed curriculum completed the pre- and postsession satisfaction and overall interest in ophthalmology questionnaires and a knowledge-based test. RESULTS: Analysis of 1640 student evaluations demonstrated an increase in ophthalmology curriculum rating following the launch of the foundations ophthalmology curriculum (p = 0.015). Among the 335 students who completed the eye dissection lab, there was a significant increase in the average scores for the satisfaction questionnaire, knowledge-based test, and level of interest in the field of ophthalmology from before and after the session, with improvements in scores noted in 91%, 42%, and 36% of the educational parameters of the participants, respectively (p < 0.001). CONCLUSIONS: The newly designed foundations ophthalmology curriculum and the eye dissection lab at the University of Toronto serve as effective means for enhancing ophthalmology teaching in medical schools across Canada.

Acute Angle Closure Following Implantable Collamer Lens for Myopia.

We report a case of acute angle closure with significantly elevated intraocular pressure 9 hours after implantation of a phakic intraocular lens for high myopia.

Small ciliary body tumors: ultrasound biomicroscopic assessment and follow-up of 42 patients.

PURPOSE: Detecting and following small tumors of the ciliary body is a particular challenge because of their location. Recently high-frequency ultrasound biomicroscopy (UBM) has been used to assist in this task. The aim of this study was to evaluate this subset of small ciliary body tumors through the use of UBM. DESIGN: Retrospective, noncomparative case series. METHODS: Forty-two patients with small ciliary body tumors (less than 4 mm) from our institution were included in the study with a median follow-up of 4.3 years. UBM was used to assess tumor characteristics including height, location, and internal and external features. The data were collected longitudinally, and statistical analysis was performed. RESULTS: Median initial tumor height was 2.05 mm (range 1.1 to 3.8 mm) as measured by UBM. By 5 years after diagnosis, five tumors (12%) exhibited growth. The overall mean growth rate was 0.026 mm per year (P = .00007). The most rapid period of growth was in the first year after diagnosis (growth rate 0.128 mm per year), after which the mean tumor size appeared to stabilize. CONCLUSIONS: UBM is a valuable tool for detecting and following small ciliary body tumors (less than 4 mm), as these lesions may go undetected by other methods. Despite the potential for local extension into the iris or choroid, few of the tumors in this study exhibited growth, suggesting that many of these tumors can be managed conservatively. UBM can be used to assess various internal tumor features; however, arriving at a specific diagnosis without histologic correlation is difficult.

Stereotactic radiotherapy in the treatment of juxtapapillary choroidal melanoma: preliminary results.

PURPOSE: To evaluate the preliminary results of stereotactic radiotherapy in the management of patients with juxtapapillary choroidal melanoma. METHODS & MATERIALS: A retrospective, consecutive case series of 28 patients with choroidal melanoma located within 2 mm of the optic nerve who were treated with stereotactic radiotherapy at Princess Margaret Hospital, Toronto, between October 1998 and May 2001. RESULTS: Median age was 62 years. Median tumor height was 4.6 mm and median maximum tumor diameter was 9.4 mm. The prescribed radiation dose was 70 Gy in five fractions over 10 days and median follow-up was 18.5 months. Posttreatment, 2 patients developed local tumor regrowth and 3 patients developed liver metastases. Actuarial rates of local tumor control, metastases, and survival at 18 months were 96%, 10%, and 94%, respectively. Actuarial rates of radiation-induced neovascular glaucoma, cataract, retinopathy, and optic neuropathy at 18 months were 20%, 29%, 30%, and 37%, respectively. A higher radiation dose to the lens was associated with an increased risk of cataract (p = 0.02). CONCLUSIONS: Stereotactic radiotherapy offers a noninvasive alternative to enucleation and brachytherapy in the management of juxtapapillary choroidal melanoma. However, further efforts are needed to optimize local tumor control and minimize radiation-induced complications.

Anterior chamber depth in plateau iris syndrome and pupillary block as measured by ultrasound biomicroscopy.

PURPOSE: To quantitatively analyze the anterior chamber depth (ACD) in patients with pupillary block and plateau iris syndrome. DESIGN: Retrospective, consecutive, observational case series. METHODS: We measured the ACD in 318 eyes of 318 patients who had been diagnosed by ultrasound biomicroscopy as having either pupillary block or plateau iris syndrome. Pupillary block patients were all preiridotomy and plateau iris patients were all postiridotomy. Anterior chamber depth was measured axially from the internal corneal surface to the lens surface using the ultrasound instrument's internal measuring capability. RESULTS: The mean ACD in patients with plateau iris syndrome (n = 181) was significantly smaller than the hypothesized normal ACD (2.04 +/- 0.30 mm vs 3.0 mm, P =.0001). The mean ACD in patients with pupillary block (n = 137) was also significantly smaller than the hypothesized normal ACD (2.17 +/- 0.30 mm vs 3.0 mm, P =.0001). The mean ACD in patients with plateau iris syndrome was significantly smaller than the ACD in patients with pupillary block (2.04 +/- 0.30 mm vs 2.17 +/- 0.30 mm, P =.001). CONCLUSIONS: Review of the literature suggests that patients with plateau iris have a normal or deeper axial ACD compared with pupillary block. This study found that the ACD associated with plateau iris syndrome is shallower than normal and also shallower than in pupillary block.

Outcomes of repeat penetrating keratoplasty and risk factors for graft failure.

PURPOSE: To compare repeat penetrating keratoplasty (PKP) with primary PKP with respect to patient characteristics, survival rates, and risk factors for graft failure. METHODS: Retrospective, consecutive, noncomparative case series of 116 patients who underwent repeat PKP and who were identified from a cohort of 696 PKPs performed by one surgeon over a 7.5-year period. RESULTS: Compared with patients who underwent primary PKP, regraft patients were 5 years older, had a higher rate of peripheral anterior synechiae (PAS), were more likely to require intraocular pressure (IOP)-lowering medications prior to surgery, were more likely to develop postoperative corneal neovascularization, were less likely to be phakic, and were more likely to undergo PKP in conjunction with a lens procedure. There was no difference between the two groups with respect to the distribution of original diagnoses leading to PKP and the rate of graft rejection. Two- and 5-year survival rates for repeat PKP were 63.9% and 45.6%, respectively. In a multivariate analysis, the original diagnosis leading to corneal transplantation, the presence of preoperative PAS, intraoperative anterior vitrectomy, and postoperative corneal neovascularization were identified as risk factors for graft failure in patients undergoing a regraft. CONCLUSIONS: Patients undergoing PKP for the first and second time share common risk factors for graft failure, namely, the original diagnosis leading to corneal transplantation, the presence of preoperative PAS, and the occurrence of postoperative corneal neovascularization. The difference in graft survival rates between the two groups can be partially explained on the basis of higher rates of the latter two risk factors among regrafts.

Dosimetric and late radiation toxicity comparison between iodine-125 brachytherapy and stereotactic radiation therapy for juxtapapillary choroidal melanoma.

PURPOSE: To compare the dose distributions and late radiation toxicities for (125)I brachytherapy (IBT) and stereotactic radiation therapy (SRT) in the treatment of juxtapapillary choroidal melanoma. METHODS: Ninety-four consecutive patients with juxtapapillary melanoma were reviewed: 30 have been treated with IBT and 64 with SRT. Iodine-125 brachytherapy cases were modeled with plaque simulator software for dosimetric analysis. The SRT dosimetric data were obtained from the Radionics XKnife RT3 software. Mean doses at predetermined intraocular points were calculated. Kaplan-Meier estimates determined the actuarial rates of late toxicities, and the log-rank test compared the estimates. RESULTS: The median follow-up was 46 months in both cohorts. The 2 cohorts were balanced with respect to pretreatment clinical and tumor characteristics. Comparisons of radiation toxicity rates between the IBT and SRT cohorts yielded actuarial rates at 50 months for cataracts of 62% and 75% (P=.1), for neovascular glaucoma 8% and 47% (P=.002), for radiation retinopathy 59% and 89% (P=.0001), and for radiation papillopathy 39% and 74% (P=.003), respectively. Dosimetric comparisons between the IBT and SRT cohorts yielded mean doses of 12.8 and 14.1 Gy (P=.56) for the lens center, 17.6 and 19.7 Gy (P=.44) for the lens posterior pole, 13.9 and 10.8 Gy (P=.30) for the ciliary body, 61.9 and 69.7 Gy (P=.03) for optic disc center, and 48.9 and 60.1 Gy (P<.0001) for retina at 5-mm distance from tumor margin, respectively. CONCLUSIONS: Late radiation-induced toxicities were greater with SRT, which is secondary to the high-dose exposure inherent to the technique as compared with IBT. When technically feasible, IBT is preferred to treat juxtapapillary choroidal melanoma.

A comparison between ¹²5Iodine brachytherapy and stereotactic radiotherapy in the management of juxtapapillary choroidal melanoma.

AIMS: To compare the treatment efficacy and radiation complications between (125)Iodine brachytherapy and stereotactic radiotherapy in the management of juxtapapillary choroidal melanoma. METHODS: Consecutive juxtapapillary melanoma patients treated with radiotherapy were included. Patients were divided into two cohorts: patients treated with (125)Iodine brachytherapy and patients with stereotactic radiotherapy. Comparison included the rates postradiotherapy local recurrence, secondary enucleation, metastasis and radiotherapy complications. Kaplan-Meier estimates were used to determine the actuarial rates, and logrank test to compare between the estimates. RESULTS: We included 94 patients with juxtapapillary melanoma treated with radiotherapy. The brachytherapy cohort included 30 patients and stereotactic radiotherapy was 64. The median follow-up was 46 months in both cohorts. No statistically significant differences existed between the two cohorts on comparing pretreatment clinical data and tumour characteristics. On comparing treatment efficacy, the actuarial rates at 50 months for tumour recurrence were 11% and 7% (p=0.61), secondary enucleation was 11% and 21% (p=0.30) and for metastasis were 4% and 16% (p=0.11), respectively. On comparing treatment complications, the actuarial rates at 50 months for cataracts were 62% and 75% (p=0.1), for neovascular glaucoma 8% and 47% (p=0.002), for radiation retinopathy 59% and 89% (p=0.0001), and for radiation papillopathy 39% and 74% (p=0.003), respectively. CONCLUSIONS: Both (125)Iodine brachytherapy and stereotactic radiotherapy demonstrate comparable efficacy in the management of juxtapapillary choroidal melanoma. However, stereotactic radiotherapy shows statistically significant higher radiation-induced ocular morbidities at 4 years postradiotherapy.

Antibiotic resistance of ocular surface flora with repeated use of a topical antibiotic after intravitreal injection.

IMPORTANCE: Treatment with intravitreal (IVT) injections has increased during the last several years as evidence has accumulated demonstrating the efficacy of anti-vascular endothelial growth factor agents in the treatment of neovascular age-related macular degeneration (AMD) and various retinal vascular diseases. Although IVT injections are generally safe, infectious endophthalmitis is a rare but devastating complication, and the risk of morbidity and vision loss from endophthalmitis is high. OBJECTIVE: To examine the change in antibiotic resistance of ocular surface flora with repeated prophylactic use of antibiotics after IVT injection for AMD. DESIGN AND SETTING: Prospective, nonrandomized cohort study in 2 tertiary academic hospitals. PARTICIPANTS: Patients 65 years and older with newly diagnosed AMD were recruited by 7 retinal specialists from July 1, 2010, through December 31, 2011. INTERVENTION: The study group received topical moxifloxacin hydrochloride for 3 days after each monthly IVT injection. MAIN OUTCOME MEASURE: Resistance to moxifloxacin and ceftazidime in cultured isolates at baseline and monthly for 3 months by change in minimal inhibitory concentration (MIC) of culture isolates was studied. RESULTS: The study group consisted of 84 patients, and the control group had 94 patients. In the study group, the baseline adjusted MIC increased (from 1.04 to 1.25 µg/mL; P = .01) as did the MIC for 50% of isolates (MIC50) (from 0.64 to 1.00 µg/mL) and the MIC for 90% of isolates (MIC90) (from 0.94 to 4.00 µg/mL). In both groups, the culture-positive rate did not change significantly when adjusted for baseline. No significant change was found in the MIC level, culture-positive rate, MIC50 level, and MIC90 level in the control group. Subgroup analysis found diabetes mellitus to be noncontributory to both the MIC and culture-positive rate. No endophthalmitis or adverse events were reported. CONCLUSIONS AND RELEVANCE: Repeated use of topical moxifloxacin after IVT injection significantly increases antibiotic resistance of ocular surface flora. We recommend that routine use of prophylactic antibiotics after IVT injection be discouraged. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01181713.

Cancer-associated nummular loss of RPE: expanding the clinical spectrum of bilateral diffuse uveal melanocytic proliferation.

This report describes a case of cancer-associated nummular retinal pigment epithelium loss associated with uterine cancer. The patient had progressive visual loss despite treatment with plasmapheresis, intravenous immunoglobulin, and local injection of corticosteroids. Clinical deterioration was corroborated by extension of the areas of retinal pigment epithelium loss, progression of cataracts, and growth of pigmented choroidal and iris lesions. Previously published cases of cancer-associated nummular retinal pigment epithelium loss did not describe the presence of cataracts or uveal melanocytic lesions. This case expands the clinical spectrum of bilateral diffuse uveal melanocytic proliferation.

Neovascular glaucoma after stereotactic radiotherapy for juxtapapillary choroidal melanoma: histopathologic and dosimetric findings.

PURPOSE: Enucleation after stereotactic radiotherapy (SRT) for juxtapapillary choroidal melanoma may be required because of tumor progression (TP) or the development of intractable radiation-induced neovascular glaucoma (NVG). We compare pathologic changes and dosimetric findings in those eyes enucleated secondary to NVG as opposed to TP to better understand potential mechanisms. METHODS AND MATERIALS: Patients with juxtapapillary choroidal melanoma treated with SRT (70 Gy in 5 fractions, alternate days over a total of 10 days) at the Princess Margaret Hospital, Toronto, Ontario, Canada, who underwent enucleation between 1998 and 2006 were selected. We correlated dosimetric data based on the patient's original SRT treatment plan with histopathologic findings in the retina, optic nerve head, and anterior chamber. A dedicated ocular pathologist reviewed each case in a blinded fashion. RESULTS: Ten eyes in ten patients were enucleated after SRT. Six were enucleated secondary to NVG and four secondary to because of TP. Aggressive tumor features such as invasion of the sclera and epithelioid cell type were observed predominantly in the TP group. Retinal damage was more predominant in the NVG group, as were findings of radiation-related retinal vascular changes of fibrinoid necrosis and hyalinization. No conclusive radiation-related effects were found in the anterior chamber. The maximum point dose and dose to 0.1 cc were lower for the anterior chamber as compared with the dose to the tumor, retina, and optic nerve head. The mean 0.1-cc doses to the retina were 69.4 Gy and 73.5 Gy and to the anterior chamber were 4.9 Gy and 17.3 Gy for the NVG group and tumor progression group, respectively. CONCLUSIONS: Our findings suggest that NVG is due to radiation damage to the posterior chamber of the eye rather than primary radiation damage to the anterior segment.

Long-term follow-up of 42 patients with small ciliary body tumors with ultrasound biomicroscopy.

PURPOSE: To establish the growth behavior of small ciliary body tumors in a relatively large cohort of patients over an extended period. DESIGN: Retrospective, noncomparative case series. METHODS: Ciliary body tumors less than 4 mm in size within the penetration power of ultrasound biomicroscopy (UBM) were included. Tumor height was assessed by ultrasound biomicroscopy. Tumor growth was defined as an increase in height of at least 20% from baseline, as measured on 2 consecutive UBM readings. The data were collected longitudinally, and a statistical analysis was performed. RESULTS: Forty-two patients were included in the study with a median follow-up of 9.0 years (range, 1.0 to 17.2 years). The median age was 59 years (range, 17 to 82 years). Median initial tumor height was 2.05 mm (range, 1.11 to 3.80 mm). The overall average rate of growth was 0.0014 mm per year (P = .68). The 5- and 10-year accumulative tumor growth rates were 12% and 29%, respectively. In the first 3 years after diagnosis, the growth rate of ciliary body lesions with an initial tumor thickness less than or equal to 2 mm was 0.054 mm per year (P = 0.0001); thereafter, tumor size appeared to stabilize. Tumors with an initial thickness greater than 2 mm showed a small but significant rate of regression of 0.0125 mm per year (P = 0.04). CONCLUSIONS: Most small tumors of the ciliary body show little growth over an extended period and can be managed conservatively without invasive diagnostic interventions. However, long-term follow-up is required. Indications for treatment include growth in height or lateral extension, extrascleral extension or the need for cataract surgery.