Predictors and significance of kidney dysfunction in patients with chronic graft-versus-host disease.

Kidney complications have been studied in allogeneic hematopoietic stem cell transplant patients but not specifically among chronic graft-versus-host disease (cGVHD) patients. Participants (n = 365) enrolled in the cross-sectional cGVHD natural history study (NCT00092235) were assessed for kidney dysfunction and overall survival. Kidney dysfunction was analyzed for associations in univariate and multivariable analyses. Kidney dysfunction (eGFR < 60) was found in 64 patients, and 29 patients had moderate-severe kidney dysfunction (eGFR < 45). Patients with kidney dysfunction were more likely treated with cyclosporine at evaluation or to have received it for GVHD prophylaxis, or prior treatment of GVHD. Patients with kidney dysfunction were less severely affected by cGVHD of skin, mouth, and joints/fascia. In multivariable modeling, history of cyclosporine use (OR = 2.19, 95% CI 1.13-4.25), angiotensin receptor blocker use (OR = 5.57, 95% CI 1.49-20.84), proteinuria (OR = 2.39, 95% CI 1.19-4.79), lower CRP (OR = 0.95, 95% CI 0.91-0.99), lower C3 (OR = 0.98, 95% CI 0.97-0.99), and lower hemoglobin (OR = 0.70, 95% CI 0.58-0.84) were jointly associated with kidney dysfunction. Overall survival was lower in those with moderate-severe kidney dysfunction (p = 0.015), demonstrating the importance of addressing kidney dysfunction in this population. The association of kidney dysfunction with less severe cGVHD suggests an etiology unrelated to cGVHD but potentially a consequence of drug-related toxicities.

Ocular Findings of Cryptococcal Meningitis in Previously Healthy Adults.

BACKGROUND: Patients with cryptococcal meningitis (CM) often have ocular manifestations; although data are describing these findings in nonimmunosuppressed, previously healthy individuals are scarce. METHODS: A retrospective chart review was performed for previously healthy patients with CM who underwent a complete ophthalmological examination within a 5-year period at the National Institutes of Health. Demographics, CSF parameters, findings on initial ophthalmological examination, and MRI abnormalities were analyzed. RESULTS: Forty-four patients within a median of 12 weeks after CM diagnosis were included in our study; 27 patients (61%) reported abnormal vision on presentation. Seventy-one percent of patients were not shunted at the time of their initial eye examination. The most common ocular abnormalities were visual field defects in 21 (66%), decreased visual acuity in 14 (38%), and papilledema in 8 (26%) patients. Intraocular pressure was within normal range in all patients. Cranial nerve defects were identified in 5 patients and optic neuropathy in 2 patients. Patients who had hydrocephalus or did not receive a ventriculoperitoneal shunt were not noted to have worse ocular abnormalities. CONCLUSIONS: The most common ocular findings in our cohort of nontransplant, non-HIV cryptococcal meningitis patients were visual field defects, decreased visual acuity, and papilledema. Our results emphasize the need for a comprehensive eye examination in patients with CM who may not always report a change in vision on presentation.

Infigratinib Reduces Fibroblast Growth Factor 23 (FGF23) and Increases Blood Phosphate in Tumor-Induced Osteomalacia.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by ectopic production of fibroblast growth factor 23 (FGF23) by phosphaturic mesenchymal tumors (PMTs). Acting on renal tubule cells, excess FGF23 decreases phosphate reabsorption and 1,25-dihydroxy-vitamin D (1,25D) production, leading to hypophosphatemia, impaired bone mineralization, pain, and fractures. Fibronectin 1-fibroblast growth factor receptor 1 (FN1-FGFR1) gene fusions have been identified as possible drivers in up to 40% of resected PMTs. Based on the presumptive role of FGFR1 signaling by chimeric FN1-FGFR1 proteins, the effectiveness of infigratinib, a FGFR1-3 tyrosine kinase inhibitor, was studied in an open-label, single-center, phase 2 trial. The primary endpoint was persistent normalization of blood phosphate and FGF23 after discontinuation. Four adults with TIO (two nonlocalized, two nonresectable PMTs) were treated with daily infigratinib for up to 24 weeks. All patients had a favorable biochemical response that included reduction in intact FGF23, and normalization of blood phosphate and 1,25D. However, these effects disappeared after drug discontinuation with biochemistries returning to baseline; no patients entered biochemical remission. In the two patients with identifiable tumors, 68Gallium (68Ga)-DOTATATE and 18Fluoride (18F)-Fluorodeoxyglucose (FDG) PET/CT scans showed a decrease in PMT activity without change in tumor size. Patients experienced mild to moderate, treatment-related, dose-limiting adverse events (AEs), but no serious AEs. Three patients had dose interruptions due to AEs; one patient continued on a low dose for the entire 24 weeks and one patient stopped therapy at 17 weeks due to an AE. The study closed early due to a failure to meet the primary endpoint and a higher-than-expected incidence of ocular AEs. Infigratinib treatment lowered FGF23, increased blood phosphate, and suppressed PMT activity, confirming the role of FGFR signaling in PMT pathogenesis. However, treatment-related AEs at efficacy doses and disease persistence on discontinuation support restricting the use of infigratinib to patients with life-limiting metastatic PMTs. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Outcomes in Previously Healthy Cryptococcal Meningoencephalitis Patients Treated With Pulse Taper Corticosteroids for Post-infectious Inflammatory Syndrome.

BACKGROUND: Cryptococcal meningoencephalitis (CM) is a major cause of mortality in immunosuppressed patients and previously healthy individuals. In the latter, a post-infectious inflammatory response syndrome (PIIRS) is associated with poor clinical response despite antifungal therapy and negative cerebrospinal fluid (CSF) cultures. Data on effective treatment are limited. METHODS: Between March 2015 and March 2020, 15 consecutive previously healthy patients with CM and PIIRS were treated with adjunctive pulse corticosteroid taper therapy (PCT) consisting of intravenous methylprednisolone 1 gm daily for 1 week followed by oral prednisone 1 mg/kg/day, tapered based on clinical and radiological response plus oral fluconazole. Montreal cognitive assessments (MOCA), Karnofsky performance scores, magnetic resonance imaging (MRI) brain scanning, ophthalmic and audiologic exams, and CSF parameters including cellular and soluble immune responses were compared at PIIRS diagnosis and after methylprednisolone completion. RESULTS: The median time from antifungal treatment to steroid initiation was 6 weeks. The most common symptoms at PIIRS diagnosis were altered mental status and vision changes. All patients demonstrated significant improvements in MOCA and Karnofsky scores at 1 month (P < .0003), which was accompanied by improvements in CSF glucose, white blood cell (WBC) count, protein, cellular and soluble inflammatory markers 1 week after receiving corticosteroids (CS) (P < .003). All patients with papilledema and visual field deficits also exhibited improvement (P < .0005). Five out of 7 patients who underwent audiological testing demonstrated hearing improvement. Brain MRI showed significant improvement of radiological findings (P = .001). CSF cultures remained negative. CONCLUSIONS: PCT in this small cohort of PIIRS was associated with improvements in CM-related complications with minimal toxicity in the acute setting.

Surgical simulator training reduces operative times in resident surgeons learning phacoemulsification cataract surgery.

PURPOSE: To compare the surgical duration for routine phacoemulsification surgeries in residents with and without virtual simulator training. METHODS: Retrospective cohort study of operative times of routine phacoemulsification cataract surgeries performed by 29 different third-year residents rotating at one academic institution. One group underwent mandatory virtual cataract surgery simulator training (SIM) in their second year of residency before starting surgeries while the other group did not undergo any simulator training (NOSIM). Outcomes measured were comparative surgical times and vitreous loss rates between groups in their third year of residency. RESULTS: 722 surgeries were included. Surgeries in the SIM group were on average 6.7 min (min) shorter compared to the NOSIM group (P = 0.0001). Although both groups required less time for surgery over the course of the academic year, regression analysis showed that NOSIM group residents overall required 17% longer time for an uncomplicated clear corneal phacoemulsification surgery (incidence rate ratio 1.17; p = 0.0001). In the final month of their residency residents in the SIM group (32.2 ± 3 min) were 9 min faster than NOSIM peers (41.2 ± 3 min mean ± SE; p = 0.02). Vitreous loss rates were 1.4% in the SIM group and 3.6% in the NOSIM group (p = 0.06). CONCLUSION AND IMPORTANCE: Early and continuous implementation of mandatory virtual simulator surgical training before starting intraocular surgeries significantly decreases operative times in third year residents learning phacoemulsification compared to non-simulator trained peers.

Ocular Adverse Events following Use of Immune Checkpoint Inhibitors for Metastatic Malignancies.

PURPOSE: To report the clinical features, severity, and management of ocular immune-related adverse events (irAEs) in the setting of immune checkpoint inhibitor therapy for metastatic malignancies. METHODS: Retrospective chart review at three tertiary ophthalmology clinics. Electronic medical records were reviewed between 2000 and 2017 for patients with new ocular symptoms while undergoing checkpoint inhibition therapy. RESULTS: Eleven patients were identified. Ocular irAEs ranged from keratoconjunctivitis sicca to Vogt-Koyanagi-Harada-like findings. Average timing of irAEs from starting checkpoint inhibitor therapy was 15.7 weeks. Ocular inflammation was successfully controlled with corticosteroids in most cases, however three patients discontinue treatment as a result of ocular inflammation with decreased visual acuity, two discontinued due to progression of metastatic disease, and one discontinued due to severe systemic irAEs. CONCLUSION: We found a wide spectrum of ocular irAEs associated with immune checkpoint inhibitors. In most cases, ocular AEs did not limit ongoing cancer treatment.

White Sclera Painted Contact Lens for Masking of Conjunctival Neovascularization and Hyperemia Following Cosmetic Eye Whitening Procedure.

We describe a case of a 37-year-old veteran with recurrent conjunctival hyperemia 5 years after an eye-whitening conjunctivectomy procedure with mitomycin C who desired to have a repeat procedure by the original surgeon. Instead, the patient was counseled and successfully fitted with white sclera painted contact lenses to mask the regrowth of his conjunctival vasculature with excellent cosmetic results and comfort. Further eye-whitening surgery was, therefore, avoided. We conclude that hand-painted white sclera contact lenses with regular ocular surface health monitoring can be offered as a cosmetic, safer, and economical alternative to patients in order to avoid eye-whitening procedures known to induce ocular ischemia.

Long-Term Outcomes of Refractive Surgery Performed During the Military.

INTRODUCTION: To evaluate the long-term refractive results of laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) performed by the military in a veteran population. MATERIALS AND METHODS: Three Department of Veterans Affairs (VA) hospital sites (Puget Sound, Buffalo, and Washington D.C.) obtained IRB approval for this multi-center study. Comprehensive ophthalmologic assessment including refraction and keratometry were obtained at the time of the long-term VA examination and compared to the patients' postoperative military records. RESULTS: Eighty patients (160 eyes) enrolled in this study. At the time of treatment, patients were 21-52 years of age. Long-term post-operative data was available from 4 to 17 years post-operatively. Fifteen percent of the treatment types were LASIK and 85% PRK. At the time of their military post-operative exam (range 3-14 months, mean 4 months), 82% of patients had uncorrected visual acuity (UCVA) of 20/20 or better, and their average manifest refraction was -0.08 D (SD ± 0.48 D). At the time of the long-term ophthalmological exam at the VA medical centers (range 4-11 years, mean of 8.2 years), 49% of patients had an UCVA of 20/20 or better and an average manifest refraction was -0.64 D (SD ± 0.69 D). CONCLUSION: This is the first long-term study evaluating refractive surgery outcomes up to 17 years in a military population. Our study demonstrates safety after refractive surgery in the military with less than 0.1D increase in myopia per year and strong keratometric stability. Other changes in the eye may be the likely cause for this observed mild refractive shift.

Eleven Years of Cataract Surgery in Veterans Without Pre-existing Ocular Comorbidities.

INTRODUCTION: In 2017, over 75,000 cataract surgeries were performed within the Veterans Health Administration System (VHA). Previous reports of outcomes of cataract surgery in veterans include patients with pre-existing ocular disease, which can affect vision. To exclude the confounding factor of pre-existing ocular comorbidities, we investigated the long-term visual outcomes and complications associated with small incision cataract surgery performed on veterans without any pre-existing eye disease. MATERIALS AND METHODS: Institutional Review Board approved cohort study with detailed retrospective chart review of all phacoemulsification (small incision) cataract surgeries performed at the Veterans Affairs Medical Center in Washington D.C. over 11 years, including all pre-and postoperative visits until postoperative month 12. RESULTS: A total of 1,513 consecutive surgical cases without any pre-existing ocular disease except the cataract were included. Vision improved significantly after cataract surgery compared to the preoperative best-corrected visual acuity (BCVA) (p = 0.0001) and remained stable over the first intra- and postoperative year. All eyes without complicated surgery and 99.1% of eyes with complications achieved 20/40 or better final vision postoperatively. The most common intra-and postoperative complications were vitreous loss (3.1%) and cystoid macular edema (CME; 1.4%). Patients with complications achieved final mean BCVA of 0.04 (20/22, vitreous loss) and 0.06 (20/23, CME) mean logMAR (Snellen). CONCLUSION: Analysis of 11 years of small incision cataract surgery in eyes without pre-existing ocular disease within the VHA showed significant improvement in vision and stability 12 months after uncomplicated and complicated surgery in veterans.

Flap-off epi-LASIK versus automated epithelial brush in PRK: a prospective comparison study of pain and reepithelialization times.

PURPOSE: To compare the effect of flap-off epi-LASIK versus automated brush epithelial removal on pain and wound healing in low myopic photorefractive keratectomy (PRK). METHODS: In this prospective intraindividual study 60 patients received surface ablation in each eye. Epithelial removal was performed by an automated brush technique in one eye (brush group) and epi-LASIK with flap removal (flap-off group) in the fellow eye. The epithelial defect size was measured daily after surgery until both eyes were reepithelialized. Postoperative pain on a scale from 0 to 6 and topical and oral analgesic medication use was recorded until the bandage contact lens was removed. RESULTS: The flap-off group had significantly less postoperative pain on days 1 (P=.0003), 2 (P=.0001), 3 (P<.0001), and 4 (P<.0001) compared to the brush group. However, the average difference in pain scores between groups was only 0.33 points out of 6. No difference was noted in the normalized overall percentage rate of healing over the first 4 days in the flap-off group (5.41±1.39%/hour) compared to the brush group (5.42±1.94%/hour) (P=.97). CONCLUSIONS: The flap-off group showed a statistically but not clinically significant advantage over the brush group in pain scores. However, no difference was noted in the percentage rate of epithelial healing time between the two groups.

Allergic fungal sinusitis with massive intracranial extension presenting with tearing.

A 24-year-old male presented with tearing, and subsequent workup and imaging showed a mass with fluid involving the nasopharynx, the paranasal sinuses, and the posterior dehiscence of the left frontal sinus intracranially compressing the frontal lobe significantly. Microscopic examination confirmed the diagnosis of allergic fungal sinusitis. Endoscopic drainage and sinostomy was performed by the otolaryngology (ear-nose-throat) service. The patient was followed 9 months postoperatively and did well with resolution of the epiphora. Although epiphora alone is an unusual presentation of allergic fungal sinusitis, ophthalmologists need to be aware of this entity, as it may invade the orbit through the sinus cavities or compress on the nasolacrimal duct before it causes other mass-related symptoms. Radiology and the characteristic histopathologic findings are the most useful in establishing the correct diagnosis.

Peripheral interstitial keratitis: a novel manifestation of ocular mastocytosis.

PURPOSE: To report a case of peripheral interstitial keratitis in a patient with mastocytosis. METHODS: Clinical case description and immunohistologic examination of biopsied ocular tissue. RESULTS: A 22-year-old woman with biopsy-proven urticaria pigmentosa, a subset of mastocytosis, presented with an active peripheral interstitial keratitis with vascularization associated with foreign body sensation and itching. Biomicroscopy of the cornea showed deep corneal inflammatory infiltrates and midstromal vascularization adjacent to a region of superior bulbar conjunctiva, which was mildly chemotic and inflamed. Topical mast cell stabilizers and a short course of topical steroids produced dramatic resolution of the lesion. Biopsy of the erythematous conjunctiva adjacent to the area of corneal inflammation showed the presence of mast cells. CONCLUSION: This is the first case of corneal inflammatory infiltration in a patient with mastocytosis. Therapy for this condition consists of a combination of topical mast cell stabilizers, topical steroids, and systemic antihistaminic therapy.