Griseofulvin Radiosensitizes Non-Small Cell Lung Cancer Cells and Activates cGAS.

Extra copies of centrosomes are frequently observed in cancer cells. To survive and proliferate, cancer cells have developed strategies to cluster extra-centrosomes to form bipolar mitotic spindles. The aim of this study was to investigate whether centrosome clustering (CC) inhibition (CCi) would preferentially radiosensitize non-small cell lung cancer (NSCLC). Griseofulvin (GF; FDA-approved treatment) inhibits CC, and combined with radiation treatment (RT), resulted in a significant increase in the number of NSCLC cells with multipolar spindles, and decreased cell viability and colony formation ability in vitro. In vivo, GF treatment was well tolerated by mice, and the combined therapy of GF and radiation treatment resulted in a significant tumor growth delay. Both GF and radiation treatment also induced the generation of micronuclei (MN) in vitro and in vivo and activated cyclic GMP-AMP synthase (cGAS) in NSCLC cells. A significant increase in downstream cGAS-STING pathway activation was seen after combination treatment in A549 radioresistant cells that was dependent on cGAS. In conclusion, GF increased radiation treatment efficacy in lung cancer preclinical models in vitro and in vivo. This effect may be associated with the generation of MN and the activation of cGAS. These data suggest that the combination therapy of CCi, radiation treatment, and immunotherapy could be a promising strategy to treat NSCLC.

EPIRETINAL MEMBRANE WITH FOVEAL HERNIATION: Visual and Surgical Outcomes.

PURPOSE: Foveal herniation occurs when neuroretinal tissue protrudes through and above the level of an epiretinal membrane. This study describes the visual symptoms and spectral domain optical coherence tomography findings associated with foveal herniation and evaluates the postoperative visual, anatomical, and surgical outcomes. METHODS: A multicenter retrospective review of patients diagnosed with epiretinal membrane identified 59 patients with preoperative foveal herniation on spectral domain optical coherence tomography. Data regarding visual symptoms, preoperative and postoperative best-corrected visual acuity (BCVA), central retinal thickness, macular volume, and size of foveal herniation were collected, and statistical analysis was performed. RESULTS: A total of 58 of the 59 patients with foveal herniation underwent surgical epiretinal membrane peeling, with foveal contour restored in 53.5% of patients after surgery. Average BCVA improved from 20/80 to 20/40 Snellen equivalent at most-recent postoperative visit (P < 0.0001). The average central retinal thickness decreased from 632 µm to 432 µm (P < 0.0001) and the average macular volume decreased from 11.3 mm3 to 9.5 mm3 (P < 0.0001) at 3 months postoperatively. Preoperatively, greater herniation height was associated with worse BCVA (P = 0.008), greater central retinal thickness (P = 0.01), retinoschisis, cystoid macular edema, foveolar detachment, ellipsoid zone abnormality, and external limiting membrane abnormalities (P < 0.05). Postoperatively, there was a decrease in retinoschisis, cystoid macular edema, foveolar detachment, ellipsoid zone, and external limiting membrane abnormality (P < 0.05) on spectral domain optical coherence tomography. CONCLUSION: Patients with larger foveal herniation height had greater preoperative central retinal thickness, worse preoperative and postoperative BCVA, and more intraretinal abnormalities on spectral domain optical coherence tomography. Surgical epiretinal membrane peeling in patients with foveal herniation resulted in a significant improvement in patients' BCVA and microstructural abnormalities.

Incidence of Delayed Vitreous Hemorrhage in Patients With Retinal Tears Associated With Bridging Vessels.

BACKGROUND AND OBJECTIVE: The purpose of this article is to determine if outcomes in patients presenting with retinal tears with bridging vessels (BVs) differ from those without BVs. PATIENTS AND METHODS: A case control study of all patients presenting with retinal tears during a 3-year period was completed. Comparisons were made between patients with and without BVs. Variables included vitreous hemorrhage (VH) at presentation, delayed VH, initial and final visual acuity, need for surgery, and retinal detachment. RESULTS: There was a significant increase in the number of patients with a VH at presentation (75% vs 28%; P < .0001), delayed VH (31% vs 7.5%; P = .001), and incidence of pars plana vitrectomy (16% vs 1.3%; P = .002) in the BV cohort. There was no significant difference in time to VH (9.4 vs 38.8 days; P = .32) or final visual acuity (20/25 vs 20/25; P = .45) between the two groups. CONCLUSIONS: The presence of a BV is an important prognostic indicator for risk of delayed VH. Documenting the presence of a BV allows for appropriate patient counseling. [Ophthalmic Surg Lasers Imaging Retina 2022;53:502-505.].

Seasonal and Environmental Variations in Endophthalmitis after Intravitreal Anti-vascular Endothelial Growth Factor Injection: A Six-year Review.

PURPOSE: To evaluate seasonal and environmental variations on the incidence and outcomes of postinjection endophthalmitis. METHODS: A single-center, retrospective cohort study was conducted including all patients diagnosed with post-injection endophthalmitis between 2013-2018. Associations between climate variables and endophthalmitis incidence were evaluated. RESULTS: Of 423,297 injections administered, seasonal distribution in spring, summer, autumn, and winter was 26%, 27%, 25%, and 22%, respectively. Of 171 cases of endophthalmitis identified, seasonal distribution over the spring, summer, autumn, and fall was 25%, 23%, 26%, and 26%, respectively. Endophthalmitis incidence was not correlated with monthly precipitation (p = 0.45), monthly snowfall (p = 0.49), or monthly temperature (p = 0.65). Worse visual outcomes at initial endophthalmitis presentation were correlated with increased precipitation level (p = 0.025) but were not correlated with snowfall level (p = 0.228) or mean monthly temperature (p = 0.132). Although there were no seasonal variations of visual acuity at endophthalmitis presentation (p = 0.894), odds of final visual acuity returning to within two lines of pre-endophthalmitis visual acuity were worse among patients with endophthalmitis diagnosed in the spring (OR, 0.041; p = 0.016). CONCLUSION: In contrast to previous work on postcataract endophthalmitis, seasonal and weather factors were not associated with post-injection endophthalmitis risk or bacterial species isolated. Visual outcomes at initial endophthalmitis presentation were correlated with precipitation, and worse visual outcomes were seen in patients who developed endophthalmitis in the spring.

Epiretinal Membrane Surgery in Eyes with Glaucoma: Visual Outcomes and Clinical Significance of Inner Microcystoid Changes.

OBJECTIVE: To investigate visual acuity (VA) outcomes and OCT-based biomarkers of vision outcomes in eyes with glaucoma undergoing pars plana vitrectomy (PPV) for idiopathic epiretinal membrane (ERM). DESIGN: Retrospective, consecutive case-control series. A previously described ERM grading scale was utilized for OCT analysis. SUBJECTS: Eyes with glaucoma undergoing PPV for idiopathic ERM. INTERVENTION: PPV with membrane peel (MP) surgery. MAIN OUTCOME MEASURES: The primary outcome was VA at postoperative month 6. Outcomes were compared to a contemporary, matched control group of eyes without concurrent glaucoma undergoing PPV for idiopathic ERM. RESULTS: A total of 103 eyes from 103 patients with ERM and glaucoma were followed for a mean (± standard deviation) of 656 (± 421) days after PPV with MP surgery. Glaucoma was classified as open angle in 98 (95.1%) eyes and closed angle in 5 (4.9%) eyes. Visual acuity improved from 0.72 ± 0.48 (20/105) to 0.55 ± 0.51 (20/71) at 6 months and to 0.50 ± 0.56 (20/63) at final follow-up (P < 0.001 for both the time points). Eyes with preoperative inner microcystoid changes (n = 59; 57.3%) had significantly worse preoperative VA, postoperative VA at month 6, and final VA compared to eyes without inner microcystoid changes (P = 0.028, 0.004, and 0.007, respectively). Eyes were then compared to a matched control group of 139 eyes without glaucoma. Eyes with ERM and glaucoma had a higher rate of microcystic changes both before surgery (P < 0.001) and at postoperative month 6 (P < 0.001), and had a worse VA at 6 months (P = 0.03) and final follow-up (P = 0.04) compared to control eyes without glaucoma. Advanced disc cupping was the only factor independently correlated with worse 6-month (P = 0.01) and final (P = 0.007) VA in multivariate analysis. CONCLUSIONS: Preoperative inner microcystoid changes on OCT were present in over half of eyes with ERM and concurrent glaucoma, and may be a poor prognostic OCT biomarker. Eyes with ERM and concurrent glaucoma experienced worse vision outcomes compared to eyes with ERM alone, particularly those with advanced disc cupping.

Outcomes of Primary Rhegmatogenous Retinal Detachment Repair in Eyes With Preoperative Grade B or C Proliferative Vitreoretinopathy.

Purpose: This work evaluates the anatomic and functional outcomes of primary rhegmatogenous retinal detachments (RRDs) with preoperative grade B and C proliferative vitreoretinopathy (PVR) vs eyes without PVR. Methods: As a multi-institutional, interventional, retrospective study of all patients undergoing primary RRD surgical procedures from January 1, 2015, through December 31, 2015, this study evaluated the visual acuity (VA) outcomes and single-surgery anatomic success rates (SSAS) of patients with primary grade B and C PVR at the time of RRD repair. Results: A total of 2486 eyes underwent primary RD surgery during the study period, of which 153 eyes (6.2%) had documented preoperative PVR grade B or C. Eyes without PVR had better SSAS compared with eyes with grade B or C PVR (87% vs 83% vs 75%, respectively, P < .0001). Eyes without PVR also had better final mean (SD) logMAR VA (0.35 [0.47]; 20/45 Snellen equivalent) than eyes with PVR of grade B (0.50 [0.56]; 20/63 Snellen equivalent) or grade C (P < .0001). In only eyes with preoperative PVR, there were no significant differences in final VA or SSAS on multivariate analysis based on surgical approach or use of retinectomy or membrane peeling alone in the intraoperative management of PVR. Conclusions: Eyes with primary preoperative grade B and C PVR appear to have significantly worse VA outcomes and lower surgical success rates. Surgical approach and management of PVR membranes did not appear to affect VA or success rates, indicating that preoperative PVR severity may dictate these outcomes.

Geographic Access Disparities to Clinical Trials in Diabetic Eye Disease in the United States.

PURPOSE: To identify geographic and socioeconomic variables predictive of residential proximity to diabetic eye disease clinical trial locations. DESIGN: Cross-sectional, retrospective study. PARTICIPANTS: De-identified census tract-level data from public datasets and trial-level data from ClinicalTrials.gov. METHODS: Using public data from ClinicalTrials.gov, we identified all active interventional clinical trials in diabetic eye disease since 2017. After geolocating every trial site, we used an origin-destination cost-matrix to calculate the driving distance and travel time from the population-weighted United States census tract centroid to the nearest site. We then used public databases to identify census tract-level socioeconomic factors predictive of driving distance and time. MAIN OUTCOME MEASURES: Driving distance > 60 miles and time traveled > 60 minutes to the nearest clinical trial site. RESULTS: In a multivariate model, driving distance of more than 60 miles had a significant association with rural versus urban location (adjusted odds ratio, 5.22; 95% confidence interval [CI], 3.75-7.26; P < 0.001), percentage of population at less than 200% of federal poverty level compared with the fourth quartile (first quartile: adjusted odds ratio, 0.40 [95% CI, 0.29-0.55]; second quartile: adjusted odds ratio, 0.60 [95% CI, 0.47-0.77]; third quartile: adjusted odds ratio, 0.76 [95% CI, 0.63-0.91]; P < 0.001) and the Midwest (adjusted odds ratio, 2.15; 95% CI, 1.13-4.07; P = 0.02), South (adjusted odds ratio, 2.71; 95% CI, 1.23-5.99; P = 0.01), and West (adjusted odds ratio, 3.01; 95% CI, 1.21-7.54; P = 0.02) regions as compared with the Northeast. Driving distance was associated with county-level prevalence of diabetes in the univariate model (odds ratio, 1.12; 95% CI, 1.06-1.19; P < 0.001), although it was nonsignificant in the multivariate model. Similar predictors were found for time traveled in minutes. CONCLUSIONS: Geographic maldistributions of clinical trial sites exist for diabetic eye disease in the United States. Those with higher travel burden are more likely to reside in a census tract that is rural, low income, and from areas outside the Northeast.

Cryptococcal Meningitis Presenting as Endophthalmitis in an Otherwise Asymptomatic Patient.

Purpose: Cryptococcus neoformans is a budding yeast that has a tropism for the central nervous system where it may cause meningitis, which has a high mortality rate. Endophthalmitis is rare and typically occurs in the setting of meningitis and disseminated disease. This report describes an atypical presentation of cryptococcal endophthalmitis and outlines the appropriate workup and management for this disease. Methods: A case report is presented. Results: A 66-year-old man on chemotherapy who presented with blurry vision without any extraocular symptoms was diagnosed with cryptococcal endophthalmitis and found to have underlying bloodstream and central nervous system infection on subsequent workup. He was treated with intravenous and intravitreal antifungals and remained systemically well, although a large subretinal mass lesion remained stable at 2-month follow-up. Conclusions: Cryptococcal endophthalmitis may be the initial presentation of disseminated cryptococcal disease. If vitreous cultures grow Cryptococcus, clinicians should presume that meningitis is present, regardless of symptoms, until proven otherwise.

Clinical Presentation of Rhegmatogenous Retinal Detachment during the COVID-19 Pandemic: A Historical Cohort Study.

PURPOSE: To investigate the effect of the coronavirus disease 2019 (COVID-19) pandemic on the clinical presentation of acute, primary rhegmatogenous retinal detachment (RRD). DESIGN: Single-center, consecutive case series with historical controls. PARTICIPANTS: Consecutive patients seeking treatment for primary RRD in a 50-day period during the COVID-19 pandemic (March 9-April 27, 2020) and the corresponding 50-day period during the previous year (March 4-April 22, 2019) in the United States. METHODS: The cohorts were compared to assess demographic variables and clinical presentations. Multivariate logistic regression was used to identify factors predictive of presenting macular attachment status. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients with macula-on RRD at presentation. Secondary outcomes included visual acuity (VA), duration of symptoms before presentation, proportion seeking treatment within 1 day of symptom onset, and presence of primary proliferative vitreoretinopathy (PVR). RESULTS: Eighty-two patients were included in the 2020 cohort compared with 111 patients in the 2019 primary control cohort. Demographic factors were similar between the groups. Significantly fewer patients demonstrated macula-on RRD in the 2020 cohort (20/82 patients [24.4%]) than in the 2019 cohort (55/111 patients [49.5%]; P = 0.001). Patients in the 2020 cohort showed worse median VA at presentation (1.00 logarithm of the minimum angle of resolution [logMAR; Snellen equivalent, 20/200] in 2020 vs. 0.48 logMAR [Snellen equivalent, 20/60] in 2019; P = 0.008), fewer patients sought treatment within 1 day of symptoms (16/80 patients [19.5%] in 2020 vs. 41/106 patients [36.9%] in 2019; P = 0.005), and a greater proportion demonstrated primary PVR (11/82 patients [13.4%] in 2020 vs. 5/111 patients [4.5%] in 2019; P = 0.03). In multivariate analysis, younger age (P = 0.03) and established patient status (P = 0.02) were independent predictors of macula-on status in the 2020 cohort. CONCLUSIONS: Patients with primary RRD during the 2020 COVID-19 pandemic were less likely to have macula-on disease and more likely to delay seeking treatment and to show worse vision and PVR.

Endophthalmitis after cataract surgery: an update on recent advances.

PURPOSE OF REVIEW: Prevention and management of postcataract endophthalmitis remain quite relevant for anterior segment and vitreoretinal surgeons. Although the Endophthalmitis Vitrectomy Study, published in 1996, remains the only level 1 evidence for the management of postcataract endophthalmitis, recent advances have resulted in an evolution of practice patterns. The aim of this review is to summarize the literature regarding postcataract endophthalmitis with a focus on the last 18 months. RECENT FINDINGS: The IRIS registry indicates the rates of endophthalmitis are decreasing in the United States, and the outcomes appear to be improving. Intracameral moxifloxacin has become more widely accepted and intracameral vancomycin has been shown to be associated with retinal vasculitis. The role of systemic antibiotics and vitrectomy is unclear and practice patterns vary widely. SUMMARY: Although practice patterns vary, prevention and treatment of endophthalmitis after cataract surgery continues to improve. More uniform guidelines regarding surgical and medical therapy are necessary but the standard of prompt referral to a vitreoretinal specialist for immediate intravitreal antibiotics remains the most important intervention in the management of postcataract endophthalmitis.

Lacrimal drainage apparatus melanoma remotely following treatment and resolution of conjunctival melanoma.

Lacrimal drainage apparatus melanoma is a rare entity that may arise primarily or, more commonly, as secondary involvement from melanoma originating elsewhere. Conjunctival melanoma may involve the lacrimal drainage apparatus (LDA) via spread along the canalicular epithelium, separate in situ processes, or direct invasion. Only seven cases exist in the literature where conjunctival melanoma remotely recurred in the LDA. We report three additional patients, two with invasive conjunctival melanoma and one with primary acquired melanosis (PAM) with severe atypia/melanoma in situ, who developed LDA melanoma at 5, 8, and 16 years after initial treatment of conjunctival melanoma. This report confirms the ability of conjunctival melanoma to give rise to spatially and temporally remote LDA melanoma despite adequate local treatment, and reviews the proposed mechanisms and associated characteristics of LDA recurrence in conjunctival melanoma.

Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma with Myxoid Stroma in a Hereditary Retinoblastoma Survivor.

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) is an indolent, locally aggressive mesenchymal neoplasm, most often confined to the lower extremities and retroperitoneum and rarely identified in the orbit. Diagnosis of ALT/WDL can be challenging due to its frequent morphologic overlap with benign adipose lesions and other more aggressive liposarcoma subtypes, including myxoid liposarcoma. We describe a 26-year-old female with a history of hereditary retinoblastoma and external-beam radiotherapy to the orbit, who developed orbital liposarcoma. Although initial morphologic assessment raised the consideration of myxoid liposarcoma, subsequent fluorescein in situ hybridization studies demonstrated MDM2 and DDIT3 coamplification without DDIT3 rearrangement, supporting the diagnosis of ALT/WDL with myxoid stroma. The literature review of previously reported orbital myxoid liposarcomas revealed a morphologic overlap of documented tumors with ALT/WDL, dedifferentiated liposarcoma, and pleomorphic liposarcoma with myxoid stroma as well as an absence of immunohistochemical and molecular genetic data supportive of the diagnosis of myxoid liposarcoma. This case emphasizes the potential overlap of ALT/WDL with myxoid liposarcoma and the increasing importance of molecular genetic studies in the diagnosis, prognosis, and management of orbital liposarcoma.

Isolated Langerhans Cell Histiocytosis of the Lacrimal Gland in Conjunction With Mucosa-Associated Lymphoid Tissue Lymphoma and Elevated IgG4 Plasma Cells.

Langerhans cell histiocytosis (LCH) is a clonal neoplastic proliferation of Langerhans-type cells. Orbital LCH is infrequent, typically manifesting as an isolated lytic bony lesion with an adjacent soft tissue mass in a child. Isolated lacrimal gland involvement by LCH is extremely rare, with only 2 previously reported cases. The authors describe a 37-year-old woman with a 6-month history of painless right upper eyelid swelling and diffuse right lacrimal gland enlargement without bony changes on computed tomography scan. Excisional biopsy of the lacrimal gland demonstrated concurrent LCH, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, and increased IgG4-expressing plasma cells. Work-up was negative for systemic hematolymphoid malignancy and IgG4-related disease. This case illustrates the association between LCH, mucosa-associated lymphoid tissue lymphoma, and elevated IgG4 plasma cells in the lacrimal gland, and we review the emerging theories proposed to explain this phenomenon.

STAT RT: a prospective pilot clinical trial of Scan-Plan-QA-Treat stereotactic body radiation therapy for painful osseous metastases.

BACKGROUND: Planning and treatment of bone metastases with palliative radiotherapy often requires 1-3 weeks, resulting in patient inconvenience and delayed palliation. We developed an expedited workflow that delivers palliative stereotactic body radiation therapy (SBRT) to painful bone metastases in which CT, planning, quality assurance (QA), and initial treatment are performed one day. This prospective pilot clinical trial evaluates the feasibility, safety, efficacy, and patient satisfaction of this workflow. METHODS: Patients with 1-3 painful bone metastases were prospectively enrolled and treated with 2-5 fractions of 5-10 Gy per fraction. Bone pain, opioid use, patient satisfaction, performance status, and quality of life were evaluated prior to and at 1, 4, 8, 12, 26, and 52 weeks post treatment. Outcomes and treatment-related toxicity were analyzed. RESULTS: Twenty-eight patients were enrolled and 37 metastases treated, receiving an average of 21.6 Gy in 3.1 fractions. Median time from CT simulation to 1st treatment was 6.6 hours. Average worst pain scores were significantly lower at all post-treatment time points with maximal response noted at 3 months. Opioid use was not significantly different from baseline at any follow up. Performance status was significantly increased only at week 12. Bone pain quality of life was significantly increased at all time points except at 52 weeks while general quality of life was significantly increased at only weeks 8 and 26. Ninety-two percent of patients reported being mostly or completely satisfied with the treatment results from week 8 until the end of follow-up. There was no grade 3 or higher toxicities. CONCLUSIONS: Results demonstrate that treating bone metastases with palliative SBRT via a multi-fraction Scan-Plan-QA-Treat patient centric workflow is feasible and safe. Although performance status, general quality of life, and opioid use were not significantly altered, patient satisfaction was high with this same-day treatment workflow.

Dexamethasone implantation in birdshot chorioretinopathy - long-term outcome.

PURPOSE: To evaluate the long-term efficacy of the 0.70 mg dexamethasone (DEX) intravitreal implant in patients with birdshot chorioretinopathy (BSCR). METHODS: Retrospective descriptive case series of BSCR patients treated with DEX implant (DEX implant 0.70 mg, DEX). Patients receiving treatment between September 2013 and November 2016 with a minimum follow-up (FU) of 12 months were included. The outcomes of primary interest were vision-related functioning, Snellen visual acuity, ocular inflammation status, presence or absence of vasculitis, change in central macular thickness, and development of glaucoma and/or cataract. Change in vision-related functioning was evaluated by comparing the National Eye Institute Visual Function Questionnaire-25. The outcomes were assessed at baseline, after DEX implant, at time of relapse, and at last FU. RESULTS: Three patients (six eyes) were included in the study and were followed for 1-3 years. They received 1-4 DEX implants OU. All patients demonstrated improvement in National Eye Institute Visual Function Questionnaire-25 scores. Mean Snellen visual acuity better than or equal to 20/40 was seen in three eyes at baseline and five eyes at last FU. At induction, all of the patients (six eyes) had active vitritis and two (four eyes) had retinal vasculitis. All three patients (six eyes) were quiet at last FU. One patient (two eyes) developed bilateral ocular hypertension requiring topical therapy and discontinuation of DEX implants. Two patients (three eyes) developed posterior subcapsular cataract during therapy. Two patients (four eyes) showed progression of disease while on DEX therapy. All patients were eventually transitioned to systemic immunosuppressive drug therapy. CONCLUSION: BSCR patients receiving DEX implant experienced clinically meaningful improvements in patient-reported visual function as well as ocular inflammation. However, patients in this study required repeat implantation and were unable to be maintained on DEX implant long term due to development of adverse effects or progression of disease. Eventually, it was necessary to transition to systemic immunosuppressive therapy in all patients.

Double vision in adults.

PURPOSE: To determine the patient characteristics, patterns in presentation and incidences of the various etiologies in adult patients with the chief complaint of double vision. DESIGN: Retrospective review. SUBJECTS: All persons greater than 18 years of age who presented to a single provider (DG) in a nonacademic private practice over a 2-year period, from 2011 to 2013, with the chief complaint of double vision. The provider is part of a multispecialty eye care group practice with both ophthalmologists and optometrists. This group practice provides a large adult referral base. METHODS: Examination for each patient included refraction, versions, alignment in different positions of gaze at distance and at near, binocular sensory testing, neuro-ophthalmologic examination, and dilated fundus examination if not recently documented. Alignment was measured with cover-uncover testing and alternate cover testing with prism bars or free prisms, using Snellen letters for fixation. Appropriate refractive correction was ensured. Alignment was measured in the primary position at distance and in gaze directed 20 degrees L, R, up, and down. The near deviation was measured in the reading position with the large letters on a near card for fixation. Sensory testing was performed with the Worth 4-dot at distance and near and with the Titmus stereopsis test. Vectograph testing was also performed at distance on many patients, particularly those with small-angle deviations. The prismatic correction necessary to correct diplopia subjectively at distance in the primary position and at near in the reading position was also recorded. PRIMARY OUTCOME: Ocular alignment and etiology of diplopia. Management, response to treatment, and outcome were also recorded. RESULTS: A total of 125 patients were included in the analysis. Subjects ranged from 18 to 93 years of age. Most cases of idiopathic strabismus were in the elderly, but the age range varied with category of underlying strabismus. Small-angle HT was the most common type of strabismus, comprising 21% of all subjects. ET, usually of the divergence insufficiency type (20%); XT (14%); and palsies not including trochlear palsy (12%) and trochlear palsy (8%) were the next most common etiologies. No strabismus was found in 11% of subjects. CONCLUSIONS: Most cases of diplopia in adults presenting as an outpatient can be classified into a few categories based on their type of strabismus. These categories of strabismus share typical age ranges and features. While diplopia in adults is usually idiopathic, diplopia can be the presenting sign of serious underlying pathology. Thus, a thorough history; examination; and, in some cases, diagnostic testing is necessary.

Macular corneal dystrophy: A review.

Macular corneal dystrophy is a corneal stromal dystrophy which leads to progressive vision loss. Macular corneal dystrophy is an autosomal recessive condition in which there is abnormality of proteoglycan synthesis. Mutations in the carbohydrate sulfotransferase gene prevent normal sulfation of corneal keratan. Different immunophenotypes have been described depending on the presence of keratan sulfate in cornea and/or serum. The deposition of abnormal proteoglycans leads to loss of corneal transparency and decreased vision. Imaging techniques such as in vivo confocal microscopy and anterior segment ocular coherence tomography have helped enhance our understanding of the corneal ultrastructural changes in this condition. These imaging modalities provide additional information without the need for a tissue biopsy or excision. Traditionally, full-thickness penetrating keratoplasty to replace the opacified cornea has remained the standard of treatment to improve vision. However, newer surgical interventions such as deep anterior lamellar keratoplasty and phototherapeutic keratectomy have also been shown to play a role in the treatment. Disease recurrence remains a challenge and the reason for poor visual prognosis. Newer techniques such as gene-targeting therapies and enzyme replacement therapies are being studied for a potential permanent solution in macular corneal dystrophy. Recent research is directed toward development of genetically modified products to integrate into host corneal DNA and block the mutant genes and hence overcome the underlying pathophysiology. Enzyme replacement therapy is another intervention with potential to treat macular corneal dystrophy. Animal studies show clearance of accumulated keratan sulfate from the body tissues in the treatment of systemic mucopolysaccharidosis by long-term enzyme replacement therapy. Future research should be directed toward elucidation of the relationship between the mutated carbohydrate sulfotransferase gene, the mechanism of deposit formation, and the development of pharmaceutical agents based on gene therapy.

Closed-Eye Visualizations in the Setting of Hyponatremia.

PURPOSE: To report a case of closed-eye visualizations and to clarify the different types of hallucinations and their etiologies. METHODS: Retrospective case report of a patient with closed-eye visualizations secondary to hyponatremia. Clinical findings, physical exam, laboratory assessment, treatment, and disease course from the patient's hospitalization were used in creating this report. Follow-up data after discharge were also obtained. RESULTS: Closed-eye visualizations were diagnosed as secondary to hyponatremia, as they did not occur with the eyes open, and potential alternate causes were excluded. Serum sodium nadir was 119 mEq/L. Symptoms resolved with correction of hyponatremia via fluid resuscitation and electrolyte replenishment. There has been no recurrence of the symptoms. CONCLUSION: This patient had hallucinations exclusively with the eyes closed, which must be differentiated from the release hallucinations seen with the eyes open in Charles Bonnet syndrome. This patient had no visual loss or retinal disease, which should be suspected in open eye hallucinations.

Timing of vitrectomy for retained lens fragments after cataract surgery.

PURPOSE: To determine the outcomes of early (less than 7 inter-operative days) versus late (7 or greater inter-operative days) vitrectomy in patients with retained lens fragments in the posterior segment after cataract surgery. METHODS: This was a retrospective review of all patients underwent pars plana vitrectomy for retained lens fragments at the University of Virginia Hospital from 2002 to 2015. RESULTS: Forty-one eyes were included in the analysis. Mean follow-up time was 25.3 months (range 3.2 months-13 years). Patients in the early vitrectomy group had poorer baseline visual acuity than those in the late vitrectomy group (mean logMAR, 1.10 vs. 0.53, p = 0.030). No other pre-operative differences existed between the two groups. At the final follow-up, there was no significant difference in visual acuity between the early (mean logMAR, 0.41) and the late (mean logMAR, 0.45) vitrectomy groups. There were no differences in rates of glaucoma, retinal detachment, or cystoid macular edema between the groups. Factors associated with final visual acuity of worse than 20/40 were diabetes mellitus, placement of anterior chamber intraocular lens at cataract surgery, cortical as opposed to nuclear retained lens fragments, post-cataract extraction complications, need for glaucoma medications, and additional surgery after vitrectomy. Separate analysis was done for patients with pre-existing eye disease resulting in worse than 20/40 vision, which showed. CONCLUSION: Clinical outcomes were similar in patients undergoing early and late vitrectomy. Patients with poorer baseline visual acuity were more likely to receive early vitrectomy. Worse final visual acuity was seen in patients with baseline diagnosis of diabetes and in those who experienced post-operative complications.