Retrospective Study of Preoperative Laser Peripheral Iridotomy Versus Intraoperative Surgical Peripheral Iridectomy in Descemet Membrane Endothelial Keratoplasty.

PURPOSE: The aim of this study was to examine the outcomes of laser peripheral iridotomy (LPI) and surgical peripheral iridectomy (SPI) for Descemet membrane endothelial keratoplasty (DMEK) and DMEK with cataract extraction (triple DMEK). METHODS: This retrospective interventional study included 135 eyes of 135 patients who underwent DMEK alone or triple DMEK. Primary outcomes were graft detachments necessitating rebubbling, repeat grafts, and pupillary block. The secondary outcomes included rejection, cystoid macular edema, uveitis, intraoperative hyphema, visual disturbances, and surgical time. RESULTS: Thirty-one eyes in the LPI group and 104 eyes in the SPI group were included. Fifty-six eyes had DMEK alone, and 79 had triple DMEK. Visually significant graft detachments occurred in 7 of 31 eyes in the LPI group versus 19 of 104 eyes in the SPI group ( P = 0.61). No statistical significance in DMEK alone versus triple DMEK groups ( P = 0.61 vs. P > 0.99). Two patients in the LPI group and 5 in the SPI group required regraft ( P = 0.66). One (3.2%) experienced pupillary block compared with 5 (4.8%) ( P = 0.99) in the LPI and SPI groups, respectively. Secondary outcomes were similar in both groups ranging from 0% to 3% ( P > 0.99). None had visual disturbances. In DMEK alone, duration of surgery was significantly shorter in the LPI versus SPI group (32.8 vs. 44.1 minutes, P = 0.02). CONCLUSIONS: This study demonstrated similar outcomes between LPI and SPI, although the LPI group had a shorter duration of surgery when DMEK was performed alone. The remainder of the outcomes demonstrated no statistically significant differences.

Characteristics of Vitamin A Deficiency Retinopathy at a Tertiary Referral Center in the United States.

PURPOSE: To explore the risk factors and fundus imaging features of vitamin A deficiency retinopathy (VADR) in an academic tertiary referral center in Atlanta, GA, United States, and to propose guidance regarding diagnostic workup and management of affected patients. DESIGN: Single-center retrospective case series. SUBJECTS: Nine patients seen between 2015 and 2021 at the Emory Eye Center diagnosed with VADR. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Baseline serum retinol level, Snellen visual acuity, multimodal fundus imaging findings, and electroretinography findings. RESULTS: Nine patients, 4 (44.4%) female, with a median (range) age of 68 (50-75) years were identified. The most common underlying etiologies for vitamin A deficiency included history of gastrointestinal surgery (55.6%), liver disease (44.4%), and nutritional depletion due to low-quality diet (44.4%). Only 1 (11.1%) patient had a history of bariatric surgery. Four (44.4%) patients were on some form of vitamin A supplementation before the diagnosis of VADR. Median (range) serum retinol level was 0.06 (< 0.06-0.19) mg/L. All patients had macular subretinal hyperreflective deposits resembling subretinal drusenoid deposits, although in some cases, these were scant and sparsely distributed. Six eyes of 3 patients with longstanding deficiency had defects in the external limiting membrane (ELM). Three of these eyes additionally had macular areas of complete retinal pigment epithelium and outer retinal atrophy (cRORA). Full-field electroretinography demonstrated severe rod dysfunction and mild to moderate cone system dysfunction. Many findings of VADR were reversible with vitamin A repletion. However, all eyes with ELM defects or cRORA had persistence or continued growth of these lesions. CONCLUSION: Vitamin A deficiency retinopathy is uncommon in the developed world. However, given that early intervention can lead to dramatic visual improvement and avoid potentially permanent retinal damage, retina specialists should be familiar with its clinical presentation. The presence of nyctalopia and subretinal hyperreflective deposits in a patient with a history of gastrointestinal surgery, liver disease, and/or poor diet can be suggestive of this diagnosis, even in the presence of ongoing vitamin A supplementation. Vitamin A supplementation can vary in route and dosage and can be tailored to the individual with serial testing of serum retinol. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Management of belantamab mafodotin-associated corneal events in patients with relapsed or refractory multiple myeloma (RRMM).

Belantamab mafodotin (belamaf) demonstrated deep and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) in DREAMM-2 (NCT03525678). Corneal events, specifically keratopathy (including superficial punctate keratopathy and/or microcyst-like epithelial changes (MECs), eye examination findings with/without symptoms), were common, consistent with reports from other antibody-drug conjugates. Given the novel nature of corneal events in RRMM management, guidelines are required for their prompt identification and appropriate management. Eye examination findings from DREAMM-2 and insights from hematology/oncology investigators and ophthalmologists, including corneal specialists, were collated and used to develop corneal event management guidelines. The following recommendations were formulated: close collaboration among hematologist/oncologists and eye care professionals is needed, in part, to provide optimal care in relation to the belamaf benefit-risk profile. Patients receiving belamaf should undergo eye examinations before and during every treatment cycle and promptly upon worsening of symptoms. Severity of corneal events should be determined based on corneal examination findings and changes in best-corrected visual acuity. Treatment decisions, including dose modifications, should be based on the most severe finding present. These guidelines are recommended for the assessment and management of belamaf-associated ocular events to help mitigate ocular risk and enable patients to continue to experience a clinical benefit with belamaf.

Optimized CorT Total to compare Scheimpflug vs dual Scheimpflug/Placido imaging devices.

PURPOSE: To compare the manufacturer-provided measures of total corneal power (TCP) generated by Scheimpflug and dual Scheimpflug/Placido imaging compared with corneal topographic astigmatism calculated on the basis of measured TCP data (CorT Total). SETTING: Emory University, Atlanta, Georgia, USA. DESIGN: Retrospective case series. METHODS: TCP values were exported from virgin 209 eyes that underwent imaging with both the Scheimpflug (Pentacam HR) and dual Scheimpflug-Placido (Galilei G4) imaging devices to compute an optimized CorT Total. The standard deviation of the ocular residual astigmatism (ORAsd), which serves as a value describing the vectoral difference between the corneal astigmatism measure and manifest refractive cylinder at the corneal plane, was evaluated for all eyes to compare manufacturer-provided measurements vs the optimized CorT Total. RESULTS: The Scheimpflug CorT Total had the lowest ORAsd (0.306 diopter [D]; spherical equivalent [SE] 0.018) of all the parameters evaluated, although the difference was not statistically significant (P = .22) from the dual Scheimpflug/Placido CorT Total (0.32 2 D; SE 0.017). For the Scheimpflug device, the CorT Total had a statistically significant lower (P < .05) ORAsd in comparison to the best measure on the device (total corneal refractive power apex zone 2 mm: 0.324 D; SE 0.021). For dual Scheimpflug/Placido measurements, the CorT Total had the lowest ORAsd (0.322 D; SE 0.017), but the difference was not statistically significant (P = .43) from the lowest manufacturer-provided measure (TCP 2). CONCLUSIONS: CorT Total generated with the Scheimpflug device corresponded better with the manifest refractive cylinder than all measures of total corneal astigmatism calculated by the software from both the Scheimpflug and the dual Scheimpflug/Placido devices.

Oral Miltefosine as Salvage Therapy for Refractory Acanthamoeba Keratitis.

PURPOSE: To report a case series of patients with treatment-resistant Acanthamoeba keratitis (AK) using oral miltefosine, often as salvage therapy. DESIGN: Descriptive, retrospective multicenter case series. METHODS: We reviewed 15 patients with AK unresponsive to therapy who were subsequently given adjuvant systemic miltefosine between 2011 and 2017. The main outcome measures were resolution of infection, final visual acuity, tolerance of miltefosine, and clinical course of disease. RESULTS: All patients were treated with biguanides and/or diamidines or azoles without resolution of disease before starting miltefosine. Eleven of 15 patients retained count fingers or better vision, and all were considered disease free at last follow-up. Eleven of 15 patients had worsening inflammation with miltefosine, with 10 of them improving with steroids. Six patients received multiple courses of miltefosine. Most tolerated oral miltefosine well, with mild gastrointestinal symptoms as the most common systemic side effect. CONCLUSIONS: Oral miltefosine is a generally well-tolerated treatment adjuvant in patients with refractory AK. The clinician should be prepared for a steroid-responsive inflammatory response frequently encountered during the treatment course.

Correction to: Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody-Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study.

The authors of the above mentioned article would like to highlight the following corrections, based upon recent changes to the FDA label and guidance on the use of belamaf.

Corneal Epithelial Findings in Patients with Multiple Myeloma Treated with Antibody-Drug Conjugate Belantamab Mafodotin in the Pivotal, Randomized, DREAMM-2 Study.

INTRODUCTION: Patients with relapsed or refractory multiple myeloma (RRMM) represent an unmet clinical need. Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class antibody-drug conjugate (ADC; or immunoconjugate) that delivers a cytotoxic payload, monomethyl auristatin F (MMAF), to myeloma cells. In the phase II DREAMM-2 study (NCT03525678), single-agent belamaf (2.5 mg/kg) demonstrated clinically meaningful anti-myeloma activity (overall response rate 32%) in patients with heavily pretreated disease. Microcyst-like epithelial changes (MECs) were common, consistent with reports from other MMAF-containing ADCs. METHODS: Corneal examination findings from patients in DREAMM-2 were reviewed, and the clinical descriptions and accompanying images (slit lamp microscopy and in vivo confocal microscopy [IVCM]) of representative events were selected. A literature review on corneal events reported with other ADCs was performed. RESULTS: In most patients receiving single-agent belamaf (72%; 68/95), MECs were observed by slit lamp microscopy early in treatment (69% had their first event by dose 4). However, IVCM revealed hyperreflective material. Blurred vision (25%) and dry eye (15%) were commonly reported symptoms. Management of MECs included dose delays (47%)/reductions (25%), with few patients discontinuing due to MECs (1%). The first event resolved in most patients (grade ≥2 MECs and visual acuity [each 77%], blurred vision [67%], and dry eye [86%]), with no reports of permanent vision loss to date. A literature review confirmed that similar MECs were reported with other ADCs; however, event management strategies varied. The pathophysiology of MECs is unclear, though the ADC cytotoxic payload may contribute to on- or off-target effects on corneal epithelial cells. CONCLUSION: Single-agent belamaf represents a new treatment option for patients with RRMM. As with other ADCs, MECs were observed and additional research is warranted to determine their pathophysiology. A multidisciplinary approach, involving close collaboration between eye care professionals and hematologist/oncologists, is needed to determine appropriate diagnosis and management of these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT03525678.

Capnocytophaga Keratitis: Clinical Presentation and Use of Metagenomic Deep Sequencing for Diagnosis.

PURPOSE: To report our experience with 2 cases of Capnocytophaga keratitis. METHODS: This is a retrospective study of case reports. We present the clinical presentation, diagnosis, and treatment strategies of 2 patients who presented with Capnocytophaga keratitis. RESULTS: Both patients had risk factors including systemic immune compromise and ocular trauma. Both patients had robust inflammatory keratitis with necrosis. Case 1 demonstrates identification of Capnocytophaga with traditional microbiologic techniques. Case 2 demonstrates the use of unbiased metagenomic deep sequencing for identification of this unusual corneal pathogen. CONCLUSIONS: Capnocytophaga is a rare and aggressive infection. Even when traditional culture identifies the pathogen rapidly, keratitis can progress to perforation. In cases of severe keratitis in which traditional culture methods are unrevealing, metagenomic deep sequencing has potential to provide actionable diagnoses.

Comparing Change in Anterior Curvature After Corneal Cross-linking Using Scanning-slit and Scheimpflug Technology.

PURPOSE: To evaluate the correlation between anterior axial curvature difference maps following corneal cross-linking (CXL) for progressive keratoconus obtained from Scheimpflug-based tomography and Placido-based topography. DESIGN: Between-devices reliability analysis of randomized clinical trial data. METHODS: Corneal imaging was collected at a single-center institution preoperatively and at 3, 6, and 12 months postoperatively using Scheimpflug-based tomography (Pentacam; Oculus Inc, Lynnwood, Washington, USA) and scanning-slit, Placido-based topography (Orbscan II; Bausch & Lomb, Rochester, New York, USA) in patients with progressive keratoconus receiving standard protocol CXL (3 mW/cm2 for 30 minutes). Regularization index (RI), absolute maximum keratometry (K Max), and change in K Max (ΔK Max) were compared between the 2 devices at each time point. RESULTS: Fifty-one eyes from 36 patients were evaluated at all time points. Values were significantly different at all time points (56.01 ± 5.3 diopters [D] Scheimpflug vs 55.04 ± 5.1 D scanning-slit preoperatively [P = .003]; 54.58 ± 5.3 D Scheimpflug vs 53.12 ± 4.9 D scanning-slit at 12 months [P < .0001]) but strongly correlated between devices (r = 0.90-0.93) at all time points. The devices were not significantly different at any time point for either ΔK Max or RI but were poorly correlated at all time points (r = 0.41-0.53 for ΔK Max, r = 0.29-0.48 for RI). At 12 months, 95% limits of agreement were 7.51 D for absolute K Max, 8.61 D for ΔK Max, and 19.86 D for RI. CONCLUSIONS: Measurements using Scheimpflug and scanning-slit Placido-based technology are correlated but not interchangeable. Both devices appear reasonable for separately monitoring the cornea's response to CXL; however, caution should be used when comparing results obtained with one measuring technology to the other.

Update in Current Diagnostics and Therapeutics of Dry Eye Disease.

Dry eye disease (DED) represents a heterogeneous group of conditions with tear film insufficiency and signs and/or symptoms of ocular surface irritation. The clinical manifestations of DED can be highly variable; hence the diagnosis is often based on a combination of symptoms, signs, and clinical tests, given that any one of these alone would miss a significant number of patients. Similarly, the treatment must often be tailored to each patient by targeting the specific mechanisms involved in his or her disease. The purpose of this review is to summarize recent advances that have allowed us to better recognize, categorize, and treat patients with DED. The most notable new diagnostic tests in DED are tear film osmolarity, inflammatory biomarkers, and meibomian gland imaging. Therapeutically, anti-inflammatory therapy, meibomian gland heating and expression, and scleral contact lenses are some of the latest options available for treating DED.

Intraocular lens alignment methods.

PURPOSE OF REVIEW: This article reviews current concepts in intraocular lens alignment strategies to maximize intraocular lens (IOL) positioning. RECENT FINDINGS: A variety of strategies has been developed to maximize toric IOL position, including preoperative calculators to determine the appropriate IOL power and orientation, intraoperative alignment devices, and postoperative software to determine if IOL rotation would be beneficial for refractive outcomes. SUMMARY: The combination of using multiple toric IOL calculators and intraoperative alignment devices has improved toric IOL outcomes. The relationship of the posterior corneal power and its effect on outcomes remains to be fully elucidated. Postoperative IOL rotation may be necessary even when the IOL is aligned as planned because of surgically induced astigmatism.

Recalcitrant Epithelial Ingrowth After SMILE Treated With a Hydrogel Ocular Sealant.

PURPOSE: To report a case of recalcitrant epithelial ingrowth after small incision lenticule extraction (SMILE) treated successfully with a novel hydrogel ocular sealant. METHODS: Case report and literature review. RESULTS: A 32-year-old man who underwent small incision lenticule extraction (SMILE) complicated by difficult lenticule extraction developed visually significant epithelial ingrowth. He then underwent two flap lifts and epithelial scrapings and flap edge suturing with recurrence of epithelial ingrowth despite these interventions. He subsequently underwent repeat scraping, followed by hydrogel ocular sealant placement (ReSure Sealant; Ocular Therapeutix, Inc., Bedford, MA), which prevented recurrence of epithelial ingrowth and reduced corneal haze. The patient was also found to have undiagnosed diabetes, suggesting that just as in LASIK, diabetes may be a risk factor for epithelial ingrowth after SMILE. CONCLUSIONS: Interface epithelial ingrowth is a potential complication after SMILE and diabetes may be a risk factor for this complication. Hydrogel ocular sealant may be effective after SMILE to prevent epithelial ingrowth into the interface.

Ocular fundus photography of patients with focal neurologic deficits in an emergency department.

OBJECTIVES: We evaluated the frequency and predictive value of ocular fundus abnormalities among patients who presented to the emergency department (ED) with focal neurologic deficits to determine the utility of these findings in the evaluation of patients with suspected TIA and stroke. METHODS: In this cross-sectional pilot study, ocular fundus photographs were obtained using a nonmydriatic fundus camera. Demographic, neuroimaging, and ABCD(2) score components were collected. Photographs were reviewed for retinal microvascular abnormalities. The results were analyzed using univariate statistics and logistic regression modeling. RESULTS: Two hundred fifty-seven patients presented to the ED with focal neurologic deficits, of whom 81 patients (32%) had cerebrovascular disease (CVD) and 144 (56%; 95% confidence interval: 50%-62%) had retinal microvascular abnormalities. Focal and general arteriolar narrowing increased the odds of clinically diagnosed CVD by 5.5 and 2.6 times, respectively, after controlling for the ABCD(2) score and diffusion-weighted imaging. These fundus findings also significantly differentiated TIA from non-CVD, even after controlling for the ABCD(2) score. CONCLUSIONS: Focal and general arteriolar narrowing were independent predictors of CVD overall, and TIA alone, even after controlling for the ABCD(2) score and diffusion-weighted imaging lesions. The inclusion of nonmydriatic ocular fundus photographs in the evaluation of patients presenting to the ED with focal neurologic deficits may assist in the differentiation of stroke and TIA from other causes of focal neurologic deficits.

Diagnostic accuracy and use of nonmydriatic ocular fundus photography by emergency physicians: phase II of the FOTO-ED study.

STUDY OBJECTIVE: During the first phase of the Fundus Photography vs Ophthalmoscopy Trial Outcomes in the Emergency Department study, 13% (44/350; 95% confidence interval [CI] 9% to 17%) of patients had an ocular fundus finding, such as papilledema, relevant to their emergency department (ED) management found by nonmydriatic ocular fundus photography reviewed by neuro-ophthalmologists. All of these findings were missed by emergency physicians, who examined only 14% of enrolled patients by direct ophthalmoscopy. In the present study, we evaluate the sensitivity of nonmydriatic ocular fundus photography, an alternative to direct ophthalmoscopy, for relevant findings when photographs are made available for use by emergency physicians during routine clinical care. METHODS: Three hundred fifty-four patients presenting to our ED with headache, focal neurologic deficit, visual change, or diastolic blood pressure greater than or equal to 120 mm Hg had nonmydriatic fundus photography obtained (Kowa nonmydriatic α-D). Photographs were placed on the electronic medical record for emergency physician review. Identification of relevant findings on photographs by emergency physicians was compared with a reference standard of neuro-ophthalmologist review. RESULTS: Emergency physicians reviewed photographs of 239 patients (68%). Thirty-five patients (10%; 95% CI 7% to 13%) had relevant findings identified by neuro-ophthalmologist review (6 disc edema, 6 grade III/IV hypertensive retinopathy, 7 isolated hemorrhages, 15 optic disc pallor, and 1 retinal vascular occlusion). Emergency physicians identified 16 of 35 relevant findings (sensitivity 46%; 95% CI 29% to 63%) and also identified 289 of 319 normal findings (specificity 91%; 95% CI 87% to 94%). Emergency physicians reported that photographs were helpful for 125 patients (35%). CONCLUSION: Emergency physicians used nonmydriatic fundus photographs more frequently than they performed direct ophthalmoscopy, and their detection of relevant abnormalities improved. Ocular fundus photography often assisted ED care even when results were normal. Nonmydriatic ocular fundus photography offers a promising alternative to direct ophthalmoscopy.

Nonmydriatic ocular fundus photography among headache patients in an emergency department.

OBJECTIVES: Determine the frequency of and the predictive factors for abnormal ocular fundus findings among emergency department (ED) headache patients. METHODS: Cross-sectional study of prospectively enrolled adult patients presenting to our ED with a chief complaint of headache. Ocular fundus photographs were obtained using a nonmydriatic fundus camera that does not require pupillary dilation. Demographic and neuroimaging information was collected. Photographs were reviewed independently by 2 neuroophthalmologists for findings relevant to acute care. The results were analyzed using univariate statistics and logistic regression modeling. RESULTS: We included 497 patients (median age: 40 years, 73% women), among whom 42 (8.5%, 95% confidence interval: 6%-11%) had ocular fundus abnormalities. Of these 42 patients, 12 had disc edema, 9 had optic nerve pallor, 6 had grade III/IV hypertensive retinopathy, and 15 had isolated retinal hemorrhages. Body mass index ≥ 35 kg/m(2) (odds ratio [OR]: 2.3, p = 0.02), younger age (OR: 0.7 per 10-year increase, p = 0.02), and higher mean arterial blood pressure (OR: 1.3 per 10-mm Hg increase, p = 0.003) were predictive of abnormal retinal photography. Patients with an abnormal fundus had a higher percentage of hospital admission (21% vs 10%, p = 0.04). Among the 34 patients with abnormal ocular fundi who had brain imaging, 14 (41%) had normal imaging. CONCLUSIONS: Ocular fundus abnormalities were found in 8.5% of patients with headache presenting to our ED. Predictors of abnormal funduscopic findings included higher body mass index, younger age, and higher blood pressure. Our study confirms the importance of funduscopic examination in patients with headache, particularly in the ED, and reaffirms the utility of nonmydriatic fundus photography in this setting.

Thermodynamic characterization of RNA triloops.

Relatively few thermodynamic parameters are available for RNA triloops. Therefore, 24 stem-loop sequences containing naturally occurring triloops were optically melted, and the thermodynamic parameters ΔH°, ΔS°, ΔG°(37), and T(M) for each stem-loop were determined. These new experimental values, on average, are 0.5 kcal/mol different from the values predicted for these triloops using the model proposed by Mathews et al. [Mathews, D. H., Disney, M. D., Childs, J. L., Schroeder, S. J., Zuker, M., and Turner, D. H. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 7287-7292]. The data for the 24 triloops reported here were then combined with the data for five triloops that were published previously. A new model was derived to predict the free energy contribution of previously unmeasured triloops. The average absolute difference between the measured values and the values predicted using this proposed model is 0.3 kcal/mol. These new experimental data and updated predictive model allow for more accurate calculations of the free energy of RNA stem-loops containing triloops and, furthermore, should allow for improved prediction of secondary structure from sequence.