New Research Aims to Optimize Therapy Against Onchocerciasis.

Onchocerciasis is a parasitic disease that is the second most common cause of infectious blindness in the world, affecting 25 million people, mostly in sub-saharan Africa. Mass drug administration (MDA) with ivermectin has been the mainstay of a successful international effort to reduce the burden of vision loss. Despite improvements in infection rates and blindness through MDA with ivermectin, adult worms are not killed or permanently sterilized by this drug and can live for greater than 10 years. Therefore, new treatments for onchocerciasis are critical to accelerating the rate of elimination of this blinding disease. Here we discuss an ongoing study of a new treatment for onchocerciasis.

Intraoperative management of posterior capsular rupture.

PURPOSE OF REVIEW: Posterior capsular rupture (PCR) and vitreous loss are inevitable complications encountered in cataract surgery across all levels of surgical experience and in spite of technological advances to improve safety. Thus, cataract surgeons must always be prepared to practice safe and effective intraoperative management strategies for capsular rupture. RECENT FINDINGS: Novel approaches for lens fragment removal, vitrectomy, and lens implantation have expanded the available options for cataract surgery in the setting of an open posterior capsule. Intraoperative PCR management strategies should prioritize safety and strive to minimize vitreous traction, stabilize anterior chamber volume, maintain capsular and zonular integrity, and protect the corneal endothelium and other anterior segment structures. SUMMARY: With appropriate management of PCR and vitreous, surgeons may still deliver safe and satisfactory visual outcomes for modern cataract surgery.

Eyelid myeloid sarcoma: ominous presentation of acute myelogenous leukemia.

A 19 year-old African American man presented to our clinic for a second opinion about a right upper eyelid mass which had been recalcitrant to treatment for nonspecific orbital inflammation by an outside facility. Examination for systemic causes of the patients eyelid lesion led to a diagnosis of acute myelogenous leukemia (AML) FAB subtype M1. A subsequent biopsy of the eyelid tumor confirmed the diagnosis of a myeloid sarcoma. The patient succumbed to complications from his leukemia within 13 months of presentation. This case report is the first, to our knowledge, of an eyelid myeloid sarcoma as the presenting sign of AML and demonstrates the poor prognosis of this lesion.

High-risk human papillomavirus-associated corneal/conjunctival intraepithelial neoplasia in a young patient.

Purpose: To report a case of high-risk human papillomavirus (HPV)-associated corneal/conjunctival intraepithelial neoplasia (CIN) in a 17-year-old fair-skinned male with no other risk factors. Observations: A 17-year-old Caucasian male presented with an 18-month history of left eye pain, redness, itchiness, and decreased vision. Examination revealed a leukoplakic nasal limbal/peripheral corneal lesion resistant to topical antibiotic and anti-inflammatory treatments. Excisional biopsy confirmed the diagnosis of CIN, and RNA in situ hybridization testing for high-risk HPV types 16/18 was positive. Subsequent testing of the patient for human immunodeficiency virus (HIV) returned negative. Conclusions and Importance: The median age of CIN diagnosis in the United States is in the sixth decade of life and is usually associated with a history of ultraviolet (UV) light exposure. There are reports of CIN in young patients with systemic immunodeficiency, immunosuppression, xeroderma pigmentosum, atopic dermatitis, asthma, and vaping. Here we present a case of high-risk HPV-associated CIN in a young, fair-skinned patient with no other identifiable risk factors.

Primary bulbar conjunctival basal cell carcinoma: A clinical-pathologic report and literature review.

Purpose: To enhance the characterization of primary bulbar conjunctival basal cell carcinoma (BCC) clinically and histologically, via report of a case and review of the relevant medical literature. Observations: We report the case of a 73-year-old man with no history of skin cancer who presented with a bulbar conjunctival nodule without connection to the eyelid or caruncle, originally thought to represent a pyogenic granuloma. After one month without improvement on topical prednisolone, excisional biopsy was performed, with routine histopathology and immunohistochemistry. The tumor was found histologically to be primary conjunctival BCC. Immunostaining exhibited negative Ber-EP4 and S100, mostly negative CK7 and EMA, and positive p63. Margins were negative, and the patient had no recurrence six months after excision. Conclusions and Importance: Primary conjunctival BCC must be considered in the differential diagnosis of a conjunctival lesion which may initially appear benign but does not behave as expected clinically. The location of the tumor in the case presented here refutes a prior postulate that primary conjunctival BCC arises from basal adnexal epithelium in the caruncle. Of the immunohistochemical findings, only the Ber-EP4 result differed from the typical immunostaining profile of cutaneous BCC. Further study is needed to determine the frequency of Ber-EP4 positivity in primary conjunctival BCC.

A randomized, open-label study of the tolerability and efficacy of one or three daily doses of ivermectin plus diethylcarbamazine and albendazole (IDA) versus one dose of ivermectin plus albendazole (IA) for treatment of onchocerciasis.

BACKGROUND: Onchocerciasis ("river blindness") has been targeted for elimination. New treatments that kill or permanently sterilize female worms could accelerate this process. Prior studies have shown that triple drug treatment with ivermectin plus diethylcarbamazine and albendazole (IDA) leads to prolonged clearance of microfilaremia in persons with lymphatic filariasis. We now report results from a randomized clinical trial that compared the tolerability and efficacy of IDA vs. a comparator treatment (ivermectin plus albendazole, IA) in persons with onchocerciasis. METHODS AND FINDINGS: The study was performed in the Volta region of Ghana. Persons with microfiladermia and palpable subcutaneous nodules were pre-treated with two oral doses of ivermectin (150 µg/kg) separated by at least 6 months prior to treatment with either a single oral dose of ivermectin 150 µg/kg plus albendazole 400 mg (IA), a single oral dose of IDA (IDA1, IA plus diethylcarbamazine (DEC. 6 mg/kg) or three consecutive daily doses of IDA (IDA3). These treatments were tolerated equally well. While adverse events were common (approximately 30% overall), no severe or serious treatment-emergent adverse events were observed. Skin microfilariae were absent or present with very low densities after all three treatments through 18 months, at which time nodules were excised for histological assessment. Nodule histology was evaluated by two independent assessors who were masked regarding participant infection status or treatment assignment. Significantly lower percentages of female worms were alive and fertile in nodules recovered from study participants after IDA1 (40/261, 15.3%) and IDA3 (34/281, 12.1%) than after IA (41/180, 22.8%). This corresponds to a 40% reduction in the percentage of female worms that were alive and fertile after IDA treatments relative to results observed after the IA comparator treatment (P = 0.004). Percentages of female worms that were alive (a secondary outcome of the study) were also lower after IDA treatments (301/574, 52.4%) than after IA (127/198, 64.1%) (P = 0.004). Importantly, some comparisons (including the reduced % of fertile female worms after IDA1 vs IA treatment, which was the primary endpoint for the study) were not statistically significant when results were adjusted for intraclass correlation of worm fertility and viability for worms recovered from individual study participants. CONCLUSIONS: Results from this pilot study suggest that IDA was well tolerated after ivermectin pretreatment. They also suggest that IDA was more effective than the comparator treatment IA for killing or sterilizing female O. volvulus worms. No other short-course oral treatment for onchocerciasis has been demonstrated to have macrofilaricidal activity. However, this first study was too small to provide conclusive results. Therefore, additional studies will be needed to confirm these promising findings. TRIAL REGISTRATION: The study is registered at Cinicaltrials.gov under the number NCT04188301.

A Reevaluation of the Tolerability and Effects of Single-Dose Ivermectin Treatment on Onchocerca volvulus Microfilariae in the Skin and Eyes in Eastern Ghana.

Mass administration of ivermectin (IVM) has significantly reduced onchocerciasis prevalence, intensity, and morbidity in most endemic areas. Most IVM clinical trials were performed long ago in persons with high-intensity infections that are uncommon in West Africa today. This cohort treatment study recruited participants from a hypoendemic area in eastern Ghana to reevaluate the efficacy and tolerability of IVM with a special focus on the kinetics of microfilaria (Mf) clearance. Mf in the skin and anterior chambers (AC) were assessed by skin snip and slit lamp examinations at baseline and at 3 and 6 months after treatment with IVM 150 µg/kg. Most participants (184-231, 79.7%) enrolled were treatment-naïve. The baseline geometric mean skin Mf count was 12.67/mg (range 3-86). Although persons with MfAC at baseline (64/231, 27%) had significantly higher skin Mf counts than people without MfAC, 7 of 39 (15%) of persons with skin Mf counts in the range of 3-5 Mf/mg had MfAC. Skin Mf were detected in 14% (31/218) and 45% (96/216) of participants 3 and 6 months after IVM treatment, respectively. MfAC were detected in 12 of 212 (5.7%) study participants at 6 months. 81% (187 of 231) of participants experienced 439 adverse events within 7 days after treatment; all adverse events were mild (96.1%) or moderate. This study has provided new data on the kinetics of Mf in the skin and eyes after IVM treatment of persons with light to moderate intensity Onchocerca volvulus infections that are common in Africa at this time.

Compositional Analysis of Extracellular Aggregates in the Eyes of Patients With Exfoliation Syndrome and Exfoliation Glaucoma.

Purpose: Exfoliation syndrome (XFS) is a condition characterized by the production of insoluble fibrillar aggregates (exfoliation material; XFM) in the eye and elsewhere. Many patients with XFS progress to exfoliation glaucoma (XFG), a significant cause of global blindness. We used quantitative mass spectrometry to analyze the composition of XFM in lens capsule specimens and in aqueous humor (AH) samples from patients with XFS, patients with XFG and unaffected individuals. Methods: Pieces of lens capsule and samples of AH were obtained with consent from patients undergoing cataract surgery. Tryptic digests of capsule or AH were analyzed by high-performance liquid chromatography-mass spectrometry and relative differences between samples were quantified using the tandem mass tag technique. The distribution of XFM on the capsular surface was visualized by SEM and super-resolution light microscopy. Results: A small set of proteins was consistently upregulated in capsule samples from patients with XFS and patients with XFG, including microfibril components fibrillin-1, latent transforming growth factor-ß-binding protein-2 and latent transforming growth factor-ß-binding protein-3. Lysyl oxidase-like 1, a cross-linking enzyme associated with XFS in genetic studies, was an abundant XFM constituent. Ligands of the transforming growth factor-ß superfamily were prominent, including LEFTY2, a protein best known for its role in establishing the embryonic body axis. Elevated levels of LEFTY2 were also detected in AH from patients with XFG, a finding confirmed subsequently by ELISA. Conclusions: This analysis verified the presence of suspected XFM proteins and identified novel components. Quantitative comparisons between patient samples revealed a consistent XFM proteome characterized by strong expression of fibrillin-1, lysyl oxidase-like-1, and LEFTY2. Elevated levels of LEFTY2 in the AH of patients with XFG may serve as a biomarker for the disease.

Corneoscleral Laceration and Ocular Burns Caused by Electronic Cigarette Explosions.

PURPOSE: To report cases of acute globe rupture and bilateral corneal burns from electronic cigarette (EC) explosions. METHODS: Case series. RESULTS: We describe a series of patients with corneal injury caused by EC explosions. Both patients suffered bilateral corneal burns and decreased visual acuity, and one patient sustained a unilateral corneoscleral laceration with prolapsed iris tissue and hyphema. A review of the scientific literature revealed no prior reported cases of ocular injury secondary to EC explosions; however, multiple media and government agency articles describe fires and explosions involving ECs, including at least 4 with ocular injuries. CONCLUSIONS: Given these cases and the number of recent media reports, ECs pose a significant public health risk. Users should be warned regarding the possibility of severe injury, including sight-threatening ocular injuries ranging from corneal burns to full-thickness corneoscleral laceration.

Use of Topical Besifloxacin in the Treatment of Mycobacterium chelonae Ocular Surface Infections.

PURPOSE: To present the clinical outcome of 3 cases of ocular surface infections by Mycobacterium chelonae treated with besifloxacin (0.6%, Besivance; Bausch & Lomb, Tampa, FL). METHODS: In this retrospective review of a small case series, we reviewed the medical records of 3 clinical patients with M. chelonae infection involving the ocular surface. Besifloxacin was used as an adjunct in 2 cases of keratitis and as the principal therapeutic agent in a case of nodular conjunctivitis. RESULTS: Two patients who presented with culture-proven M. chelonae keratitis initially had been treated with topical amikacin and oral clarithromycin for 6 months in the first case and for 2 months in the second without complete resolution. Topical besifloxacin was added as an adjunct therapy to amikacin with progressive weaning of clarithromycin. Both cases of keratitis eventually resolved without recurrence after discontinuation of topical amikacin and besifloxacin. A third patient presented with nodular conjunctival inflammation, which initially had been treated with topical ciprofloxacin and corticosteroids without improvement. One nodular lesion was excised and submitted for microbial culture, which revealed the growth of M. chelonae. Marked improvement of the conjunctivitis was noted after 3 weeks of treatment with topical besifloxacin. Complete resolution of the conjunctival nodules was achieved after 10 weeks of treatment with besifloxacin. CONCLUSIONS: Topical besifloxacin seems to be a useful adjunct agent in the treatment of nontuberculous mycobacterial keratitis by M. chelonae and may be viable for use as a first-line agent in cases of nodular conjunctivitis by M. chelonae.