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PurposeMulticentric osteolysis nodulosis and arthropathy (MONA) syndrome is a rare autosomal recessive skeletal dysplasia. Caused by mutations in the matrix metalloproteinase 2 gene (MMP2) on chromosome 16q12, this syndrome has infrequently been associated with ophthalmic manifestations. Corneal opacities have been reported but not described or documented in detail.MethodsComplete ophthalmologic examination and multimodal anterior segment imaging were used to characterize the corneal findings in a patient with MONA syndrome.ResultsA 19-year-old with MONA syndrome was referred for an eye exam based upon MONA screening recommendations. Visually insignificant peripheral corneal opacities were noted. Anterior segment optical coherence tomography (AS-OCT) demonstrated posterior stromal and endothelial hyperreflectivity. Confocal microscopy demonstrated an acellular peripheral endothelium with a normal central endothelium.ConclusionsCorneal opacities can occur with MONA syndrome, which is caused by mutations in the MMP2 gene. In the patient presented here, the corneal opacities are peripheral, deep stromal, with sparing of the anterior stroma and epithelium.

PurposeTo report a case of Light Adjustable Lens™ (LAL, RxSight, Aliso Viejo, CA) implantation in a patient with bilateral 50-cut radial keratotomy (RK) and discuss related preoperative, intraoperative, and postoperative considerations.MethodsA 78-year-old patient with history of bilateral 50-cut RK underwent phacoemulsification with implantation of LALs in both eyes one month apart. Although LAL technology was not approved specifically for addressing limitations in intraocular lens calculation post-RK due to corneal topography irregularity, the patient opted for this lens due to its ability to make post-operative adjustments to its refractive power. At postoperative month one following the second eye surgery, YAG capsulotomy was performed in both eyes. At postoperative month two following the second eye surgery, the patient began LAL adjustments spaced 1-2 weeks apart for a total of 2 LAL adjustments and 2 lock-in sessions.ResultsOur patient achieved a final refraction of -0.25 +0.25 × 110 with an UDVA of 20/20-2 in the right eye and -0.25 +0.50 × 135 with an UDVA 20/25-1 in the left eye.ConclusionsThe LAL may be a promising option for patients undergoing cataract surgery after RK, although further studies are needed to understand long-term changes in eyes with RK and the inability of LAL to address all aspects of corneal aberration.

Purpose of reviewThis study is to highlight the incidence of corneal pseudomicrocysts in FDA-approved antibody-drug conjugates (ADCs), and success of preventive therapies for pseudomicrocysts and related ocular surface adverse events (AEs).Recent findingsADCs are an emerging class of selective cancer therapies that consist of a potent cytotoxin connected to a monoclonal antibody (mAb) that targets antigens expressed on malignant cells. Currently, there are 11 FDA-approved ADCs with over 164 in clinical trials. Various AEs have been attributed to ADCs, including ocular surface AEs (keratitis/keratopathy, dry eye, conjunctivitis, blurred vision, corneal pseudomicrocysts). While the severity and prevalence of ADC-induced ocular surface AEs are well reported, the reporting of corneal pseudomicrocysts is limited, complicating the development of therapies to prevent or treat ADC-related ocular surface toxicity.SummaryThree of 11 FDA-approved ADCs have been implicated with corneal pseudomicrocysts, with incidence ranging from 41 to 100% of patients. Of the six ADCs that reported ocular surface AEs, only three had ocular substudies to investigate the benefit of preventive therapies including topical steroids, vasoconstrictors, and preservative-free lubricants. Current preventive therapies demonstrate limited efficacy at mitigating pseudomicrocysts and other ocular surface AEs.

ABSTRACT: Background: Mind-body treatments have the potential to manage pain, yet their effectiveness when delivered online for the treatment of low back pain (LBP) is unknown. We sought to evaluate whether a virtually delivered mind-body program integrating tai chi, qigong, and meditation (VDTQM) is effective for treating LBP. Methods: This randomized controlled trial compared VDTQM (n=175) to waitlist control (n=175). Eligible participants were at least 18 years old, had LBP for at least 6 weeks, were not pregnant, had not previously taken tai chi classes, and had not undergone spine surgery within 6 months. The treatment group received a 12-week VDTQM program in live online 60-minute twice-weekly group classes from September 2022 to December 2022. All participants continued their usual activities and care. Primary outcome was pain-related disability assessed by the Oswestry Disability Index (ODI) score. Secondary outcomes included pain intensity, sleep quality, and quality of life (QOL). Intent-to-treat analyses were conducted. Results: Of the 350 participants 278 (79%) were female, mean age was 58.8 years (range: 21–92), 244 (69.7%) completed the 8-week survey, 248 (70.9%) the 12-week, and 238 (68%) the 16 -week. No participants withdrew due to adverse treatment effects. Compared with control group, treatment group experienced statistically and clinically significant improvement in ODI score by −4.7 (95% CI: −6.24 to −3.16, p

PurposeThe purpose of this study was to investigate the social determinants of health for keratoconus.MethodsIn this retrospective cohort study of patients with keratoconus, the electronic health record was reviewed for keratometry, treatments received, clinical comorbidities, and social characteristics. Outcomes included severe keratoconus at presentation (steep keratometry ≥52 diopters), disease progression (≥0.75 diopters increase from the first to the most recent clinical visit), and corneal transplantation. Logistic regression was used to evaluate factors associated with severity at presentation and corneal transplantation. Cox proportional hazards modeling was used to evaluate progression.ResultsA total of 1038 patients with keratoconus were identified, 725 (70%) of whom had baseline imaging. Compared with commercially insured patients, Medicaid recipients were more likely to have severe keratoconus, independent of social and clinical confounders [odds ratio (OR) 1.94, 95% confidence interval (CI), 1.12-3.35, P = 0.017]. Male sex was independently associated with progression (hazard ratio = 1.38, 95% CI, 1.03-1.84, P = 0.030). Medicare and Medicaid recipients were more likely to require transplantation compared with commercially insured patients (OR 2.71, 95% CI, 1.65-4.46, P < 0.001 and OR 1.74, 95% CI, 1.08-2.80, P = 0.022, respectively). Other social determinants of health, including non-White race/ethnicity, limited English proficiency, and unemployment, were associated with the outcomes only in univariate analysis. Obstructive sleep apnea, atopy, body mass index, and tobacco use were not associated with any outcome.ConclusionsSocioeconomic factors were more consistent predictors of keratoconus severity and corneal transplantation compared with clinical factors that have received relatively greater attention in the keratoconus literature.

PurposeTo assess the impact of parental socioeconomic status and keratoconus literacy on pediatric eye rubbing and keratoconus severity.MethodsIn this mixed-methods study, pediatric keratoconus patients (age ≤ 18 years) were retrospectively identified. Sociodemographic and clinical characteristics were extracted from the electronic medical record (EMR). Telephone surveys were subsequently conducted to assess parental keratoconus literacy, receipt of counseling on keratoconus prevention, eye rubbing, and household socioeconomic factors not available in the EMR. Parents reporting poor keratoconus literacy were probed via semi-structured interview to explore barriers to their understanding.ResultsForty-eight patients met inclusion criteria, 22 (46%) of whom were reached by telephone. Most patients were insured by Medicaid (73%) and current eye rubbers (82%). Few parents reported good or excellent keratoconus literacy now (32%) or at the time of diagnosis (18%). Parents with a high-school education, limited English proficiency, lower income level, and Medicaid insurance tended to have lower keratoconus literacy, though this was not statistically significant. Parental keratoconus literacy was not correlated with disease severity. High-school education, limited English proficiency, lower income level, and Medicaid insurance were correlated with steeper keratometry readings, which was statistically significant for high-school education. In-depth interviews revealed parents felt unconfident with eye health in general and perceived a personal responsibility for learning more.ConclusionThis is the first study exploring keratoconus literacy from a socioeconomic perspective, demonstrating lower literacy among socioeconomically marginalized parents and a tendency toward more severe disease in their children.

PurposeTo describe trends in the use of corneal topography and tomography for the management of keratoconus patients at a single academic institution and to identify how these trends may be associated with different procedural interventions.Patients and methodsIn this retrospective cohort study, keratoconus patients treated from 2012 to 2019 were identified. The electronic health record was reviewed for the presence of corneal topography or tomography imaging completed within seven days of the first visit and the highest level of intervention at the first and most recent visit. Patients were grouped as pediatric (

PurposeTo study the feasibility and efficacy of a new remote wet lab for microsurgical education using a corneal suturing task.SettingDepartment of Ophthalmology, University of California San Francisco, San Francisco, California, USA.DesignProspective randomized controlled study.MethodsTen ophthalmology residents were stratified by postgraduate year and randomized to perform a corneal suturing task consisting of placing the 4 cardinal sutures for a penetrating keratoplasty in porcine eyes with or without remote ophthalmology attending feedback. Subsequently, both groups repeated the same task without remote feedback to test whether initial remote feedback affected subsequent performance. Finally, the group without feedback was crossed over to repeat the same corneal suturing task with remote feedback. The effectiveness of the remote wet lab was assessed subjectively by survey and objectively by grading each suture pass.ResultsResident-reported comfort with corneal suturing improved significantly after the remote wet lab for all residents. Residents and attendings rated the remote wet lab as equally or more effective compared with previous in-person wet labs and overall effective in corneal suturing. Attendings rated the remote wet lab as effective in multiple domains of microsurgical education using a modified microsurgical global rating scale. Objective corneal suturing performance was similar for both groups.ConclusionsThe remote wet lab was feasible and effective for training ophthalmology residents in corneal suturing. This represents a new social distancing compliant platform for microsurgical education during the COVID-19 pandemic.

PurposeThe epithelium lining the ocular surface, which includes corneal and conjunctival epithelia, expresses the prosecretory chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) and the proabsorptive epithelial sodium channel (ENaC). Here, methodology was established to measure the millivolt (mV) potential differences at the ocular surface, called ocular surface potential difference (OSPD), in human subjects produced by ion transport.MethodsOSPD was measured in human subjects in which a fluid-filled measuring electrode contacted a fluid pool created by eversion of the lateral lower eyelid, with a reference electrode placed subcutaneously in the forearm. Through the use of a high-impedance voltmeter, OSPD was measured continuously over 10 to 15 minutes in response to a series of perfusate fluid exchanges.ResultsBaseline OSPD (± SEM) in six normal human subjects was -21.3 ± 3.6 mV. OSPD depolarized by 1.7 ± 0.6 mV following the addition of the ENaC inhibitor amiloride, hyperpolarized by 6.8 ± 1.5 mV with a zero chloride solution, and further hyperpolarized by 15.9 ± 1.6 mV following CFTR activation by isoproterenol. The isoproterenol-induced hyperpolarization was absent in two cystic fibrosis subjects lacking functional CFTR. OSPD measurement produced minimal epithelial injury.ConclusionsOur results establish the feasibility and safety of OSPD measurement in humans and demonstrate robust CFTR activity, albeit minimal ENaC activity, at the ocular surface. OSPD measurement may be broadly applicable to investigate fluid transport mechanisms and test drug candidates to treat ocular surface disorders.Translational relevanceTo the best of our knowledge, this is the first measurement of the electrical potential generated by the ocular surface epithelium in human subjects, offering a new approach to study ocular surface function and health.

Purpose: Dry eye disorders are a major health care burden. We previously reported the identification of N-methyl-N-phenyl-6-(2,2,3,3-tetrafluoropropoxy)-1,3,5-triazine-2,4-diamine [cystic fibrosis transmembrane conductance regulator (CFTR)act-K267], which activated human wild-type CFTR chloride conductance with EC50 ∼ 30 nM. Here, we report in vivo evidence for CFTRact-K267 efficacy in an experimental mouse model of dry eye using a human compatible ophthalmic vehicle. Methods: CFTR activation in mice in vivo was demonstrated by ocular surface potential difference (OSPD) measurements. Ocular surface pharmacodynamics was measured in tear fluid samples obtained at different times after topical administration of CFTRact-K267. Dry eye was produced by lacrimal duct cautery (LDC) and corneal epithelial injury and was assessed by Lissamine green (LG) staining. Results: OSPD measurements demonstrated a hyperpolarization of -8.6 ± 3 mV (standard error of the mean, 5 mice) in response to CFTRact-K267 exposure in low chloride solution that was reversed by a CFTR inhibitor. Following single-dose topical administration of 2 nmol CFTRact-K267, tear fluid CFTRact-K267 concentration was >500 nM for more than 6 h. Following LDC, corneal surface epithelial injury, as assessed by LG staining, was substantially reversed in 10 of 12 eyes receiving 2 nmol CFTRact-K267 3 times daily starting on day 2, when marked epithelial injury had already occurred. Improvement was seen in 3 of 12 vehicle-treated eyes. Conclusion: These studies provide in vivo evidence in mice for the efficacy of a topical, human use compatible CFTRact-K267 formulation in stimulating chloride secretion and reversing corneal epithelial injury in dry eye.

Background:. Sirenomelia is a rare congenital condition characterized by fusion of the lower limbs. Patients with sirenomelia generally do not survive long after birth because the condition is associated with multisystem organ dysfunction due to developmental anomalies. Considering the low incidence and few cases surviving the neonatal period, there is minimal understanding regarding the surgical management of sirenomelia. We present a unique case of an infant born with type 1 sirenomelia, absence of external genitalia, presence of a cloaca, absence of the bladder, and presence of an imperforate and vestigial anus, who not only survived the birth process, but, at the age of 11 months, was determined to be a candidate for surgical separation of the lower extremities. Methods:. This case was approached much like a dorsal rectangular flap syndactyly release. Large Z-plasty flaps were designed and raised, and the soft tissue within the skin bridge was meticulously dissected to preserve anatomy and to provide adequate skin flaps without perineal skin grafting. A quadrangular flap was designed to reconstruct the perineum and produce a neo-vulva using de-epithelialization. Results:. Successful lower extremity separation was achieved. There were no major postoperative complications. The patient progressed with lower extremity function, and eventually achieved independent ambulation. Conclusions:. Management of sirenomelia is incredibly challenging, and data to guide surgical management are limited. This report details our approach to a successful lower extremity separation, repair, and neo-vulvar reconstruction in a case of type I sirenomelia.

Objective: To evaluate high-frequency (10-kHz) spinal cord stimulation (SCS) treatment in refractory painful diabetic neuropathy. Patients and Methods: A prospective, multicenter randomized controlled trial was conducted between Aug 28, 2017 and March 16, 2021, comparing conventional medical management (CMM) with 10-kHz SCS+CMM. The participants had hemoglobin A1c level of less than or equal to 10% and pain greater than or equal to 5 of 10 cm on visual analog scale, with painful diabetic neuropathy symptoms 12 months or more refractory to gabapentinoids and at least 1 other analgesic class. Assessments included measures of pain, neurologic function, and health-related quality of life (HRQoL) over 12 months with optional crossover at 6 months. Results: The participants were randomized 1:1 to CMM (n=103) or 10-kHz SCS+CMM (n=113). At 6 months, 77 of 95 (81%) CMM group participants opted for crossover, whereas none of the 10-kHz SCS group participants did so. At 12 months, the mean pain relief from baseline among participants implanted with 10-kHz SCS was 74.3% (95% CI, 70.1-78.5), and 121 of 142 (85%) participants were treatment responders (≥50% pain relief). Treatment with 10-kHz SCS improved HRQoL, including a mean improvement in the EuroQol 5-dimensional questionnaire index score of 0.136 (95% CI, 0.104-0.169). The participants also reported significantly less pain interference with sleep, mood, and daily activities. At 12 months, 131 of 142 (92%) participants were “satisfied” or “very satisfied” with the 10-kHz SCS treatment. Conclusion: The 10-kHz SCS treatment resulted in substantial pain relief and improvement in overall HRQoL 2.5- to 4.5-fold higher than the minimal clinically important difference. The outcomes were durable over 12 months and support 10-kHz SCS treatment in patients with refractory painful diabetic neuropathy. Trial registration: clincaltrials.gov Identifier: NCT03228420

Using multimodal imaging, we demonstrate a classic iris melanocytoma presenting with recurrent, spontaneous hyphema in a young female patient. The patient has been observed without tumor growth. Hyphema has not been previously reported to occur with iris melanocytoma.

ABSTRACT Background Temsirolimus is an mTOR antagonist with proven anticancer efficacy. Preclinical data suggest greater anticancer effect when mTOR inhibitors are combined with cytotoxic chemotherapy. We performed a Phase I assessment of the combination of temsirolimus and capecitabine in patients with advanced solid tumors. Methods Patients were enrolled in an alternating dose escalation of temsirolimus (at 15 or 25 mg IV weekly) and capecitabine (at 750, 1000, and 1250 mg/m2 twice daily) in separate Q2‐week and Q3‐week cohorts. At the recommended Phase II doses (RP2Ds) of temsirolimus and capecitabine (Q2), seven patients were also treated with oxaliplatin (85 mg/m2, day 1) to determine triplet combination safety and efficacy. Results Forty‐five patients were enrolled and 41 were evaluable for dose‐limiting toxicities (DLTs). The most common adverse events (AEs) were mucositis, fatigue, and thrombocytopenia. The most common grade 3/4 AEs were hypophosphatemia and anemia. Five patients had DLTs, including hypophosphatemia, mucositis, and thrombocytopenia. The RP2Ds were temsirolimus 25 mg +capecitabine 1000 mg/m2 (Q2); and temsirolimus 25 mg +capecitabine 750 mg/m2 (Q3). Of the 38 patients evaluable for response, one had a partial response (PR) and 19 had stable disease (SD). The overall disease control rate was 52%. Five of the 20 patients with SD/PR maintained disease control for >6 months. Conclusions The combination of temsirolimus and capecitabine is safe on both a Q2‐week and a Q3‐week schedule. The combination demonstrated promising evidence of disease control in this highly refractory population and could be considered for testing in disease‐specific phase II trials.

Purpose: To assess visual outcomes and patient satisfaction for senior resident-performed immediate sequential bilateral cataract surgery (ISBCS) versus delayed sequential bilateral cataract surgery (DSBCS) during the COVID-19 pandemic, when minimizing healthcare-related exposures for patients and providers are paramount. Methods: This was a pilot retrospective cohort study of all ISBCS and DSBCS patients who underwent senior resident-performed cataract surgery from May to September 2020 at a single academic institution. Outcome measures were final corrected distance visual acuity (CDVA), final manifest refraction (MRx), intraoperative and postoperative complications rates, total number of visits, and patient satisfaction assessed postoperatively by telephone questionnaire. Results: Twenty-two eyes of 14 patients and 56 eyes of 28 patients underwent senior resident-performed ISBCS and DSBCS, respectively. Final CDVA was 20/25 or better in 21 (95%) ISBCS and 51 (91%) DSBCS eyes (P = 0.670). Deviation of final MRx from target refraction was within 0.50 D in 17 (77%) ISBCS and 47 (84%) DSBCS eyes (P = 0.522). There was no significant difference in intraoperative (P = 1.000) or postoperative (P = 1.000) complications. ISBCS patients averaged 3.5 fewer visits than DSBCS patients (5.9 vs 9.5, P < 0.001). All ISBCS and 20 DSBCS patients (87%) reported they were “very satisfied” or “satisfied” with their experience (P = 0.701). Five of six senior residents responded that they preferred performing ISBCS over DSBCS. Conclusion: This early experience suggests that senior resident-performed ISBCS is as safe and effective as DSBCS, with the added benefit of averaging fewer in-person visits. Residency programs should consider offering senior resident-performed ISBCS to select patients during the COVID-19 pandemic.