October 2017

Massachusetts health care facilities reported a series of cataract surgery-related adverse events (AEs) to the state in recent years, including 5 globe perforations during eye blocks performed by 1 anesthesiologist in a single day. The Betsy Lehman Center for Patient Safety, a nonregulatory Massachusetts state agency, responded by convening an expert panel of frontline providers, patient safety experts, and patients to recommend strategies for mitigating patient harm during cataract surgery. The purpose of this article is to identify contributing factors to the cataract surgery AEs reported in Massachusetts and present the panel's recommended strategies to prevent them. Data from state-mandated serious reportable event reports were supplemented by online surveys of Massachusetts cataract surgery providers and semistructured interviews with key stakeholders and frontline staff. The panel identified 2 principal categories of contributing factors to the state's cataract surgery-related AEs: systems failures and choice of anesthesia technique. Systems failures included inadequate safety protocols (48.7% of contributing factors), communication challenges (18.4%), insufficient provider training (17.1%), and lack of standardization (15.8%). Choice of anesthesia technique involved the increased relative risk of needle-based eye blocks. The panel's surveys of Massachusetts cataract surgery providers show wide variation in anesthesia practices. While 45.5% of surgeons and 69.6% of facilities reported increased use of topical anesthesia compared to 10 years earlier, needle-based blocks were still used in 47.0% of cataract surgeries performed by surgeon respondents and 40.9% of those performed at respondent facilities. Using a modified Delphi approach, the panel recommended several strategies to prevent AEs during cataract surgery, including performing a distinct time-out with at least 2 care-team members before block administration; implementing standardized, facility-wide safety protocols, including a uniform site-marking policy; strengthening the credentialing and orientation of new, contracted and locum tenens anesthesia staff; ensuring adequate and documented training in block administration for any provider who is new to a facility, including at least 10 supervised blocks before practicing independently; using the least invasive form of anesthesia appropriate to the patient; and finally, adjusting anesthesia practices, including preferred techniques, as evidence-based best practices evolve. Future research should focus on evaluating the impact of these recommendations on patient outcomes.

Massachusetts state agencies received reports of 37 adverse events (AEs) involving cataract surgery from 2011 to 2015. Fifteen were anesthesia related, including 5 wrong eye blocks, 3 cases of hemodynamic instability, 2 retrobulbar hematoma/hemorrhages, and 5 globe perforations resulting in permanent loss of vision. While Massachusetts' reported AEs likely underrepresent the true number of AEs that occur during cataract surgery, they do offer useful signal data to indicate the types of patient harm occurring during these procedures.

Superior oblique myokymia (SOM) is a rare condition of unclear etiology. We discuss the history, etiology, clinical features, differential diagnoses, management and prognosis of SOM. We conducted a meta-analysis of all 116 cases published since SOM was first described in 1906. The age at examination was 17-72 years (mean 42 years.) There was a right-sided preponderance in 61% of cases (P < 0.02) that was statistically significant in females (63%, P < 0.04) but not in males (59%, P = 0.18). The pathophysiology of SOM may be neurovascular compression and/or ephaptic transmission. Although various pharmacological and surgical approaches to SOM treatment have been proposed, the rarity of the condition has made it impossible to conduct clinical trials evaluating the safety and efficacy of these approaches. Recently, topical beta-blockers have managed SOM symptoms in a number of cases, including the first case treated with levobunolol. Systemic medications, strabismus surgery, and neurosurgery have been used to control symptoms, with strabismus surgery carrying a moderate risk of post-operative diplopia in down-gaze. While there is no established treatment for SOM, we encourage clinicians to attempt topical levobunolol therapy before considering systemic therapy or surgery.

PURPOSE: To report the novel use of combined intravitreal and systemic antibiotic therapy in a patient with syphilitic panuveitis and discuss the management of ocular syphilis. METHODS: Case report Results: A 45-year old heterosexual male with human immunodeficiency virus (HIV) presented with 1 month of blurry vision in both eyes. Clinical examination revealed a bilateral panuveitis. The patient denied history of genital lesions or rash, but did complain of difficulty hearing bilaterally. Treponemal EIA was positive, the RPR titer greater than 1:512 dilution, and CSF VDRL 1:4. A diagnosis of neurosyphilis and ocular syphilis was made based on the clinical and laboratory findings. The patient was admitted for systemic intravenous antibiotic therapy, but was noted to have a penicillin allergy. Intravitreal ceftazidime was promptly administered bilaterally to achieve treponemacidal levels of antibiotic therapy. After penicillin desensitization protocol, the patient received 14 days of intravenous penicillin with clinical resolution. CONCLUSIONS: There are increasing reports of ocular syphilis in the United States and delay in diagnosis and management can lead to severe visual impairment and blindness. We report the first case of adjunct intravitreal antibiotic therapy in a penicillin allergic patient. As ocular syphilis is a form of bacterial endophthalmitis, combination intravitreal and systemic antibiotics may be considered.

Over a 2 year period a 32-year-old woman developed swellings of all 4 eyelid margins accompanied by complete loss of eyelashes. An inflammatory dermatologic condition was considered the most likely cause. A full thickness right lower eyelid biopsy revealed a multinodular lymphoid tumor at the eyelid margin which immunophenotypically and genetically was diagnosed as an extranodal marginal zone lymphoma. The mode of presentation of the disease was considered to be most unusual, as was its B cell lineage, since the majority of primary cutaneous lymphomas are of T-cell origin. Systemic workup demonstrated bilateral involvement of the external auditory canals.

PURPOSE: To report the characteristics of infection and prognostic factors of endogenous endophthalmitis (EE) over an 11-year period. METHODS: The clinical records of 41 eyes of 36 patients diagnosed with culture-proven EE at the Rajavithi Hospital were retrospectively reviewed. RESULTS: Median age at presentation was 58 years. Liver abscess (19%) and urinary tract infections (19%) were the most common sources of infection. The most common causative agents were gram-negative organisms (48%). The most commonly isolated microorganism was Klebsiella pneumoniae (26.8%). Worse initial visual acuity and severe intraocular inflammation at first presentation were equally associated with poor visual outcome in the multivariate model (adjusted odds ratio, 20.32; 95% confidence interval [1.12-357.45]; P = 0.040). CONCLUSIONS: Endogenous endophthalmitis usually has a poor visual prognosis. Liver abscess and urinary tract infections are common primary sites of infection. Poor initial visual acuity and severe intraocular inflammation at the initial presentation are predictors of poor visual outcome.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as growth, metabolism, angiogenesis and differentiation. After very preterm birth, energy demands increase while maternal supplies of nutrients and other factors are lost and the infant may become dependent on parenteral nutrition for weeks. Low postnatal IGF-1 concentrations in preterm infants are associated with poor weight gain, retinopathy of prematurity (ROP) and other morbidities. We will describe the process by which we aim to develop supplementation with recombinant human (rh) IGF-1 and its binding protein rhIGFBP-3 as a possible therapy to promote growth and maturation and reduce morbidities in extremely preterm infants. METHODS: In order to calculate a dose of IGF-1 tolerated by neonates, a pharmacokinetic study of transfusion with fresh frozen plasma was performed, which provided a relatively low dose of IGF-1, (on average 1.4 μg/kg), that increased serum IGF-1 to levels close to those observed in fetuses and preterm infants of similar GAs. Thereafter, a Phase I 3 hours IV infusion of rhIGF-1/rhIGFBP-3 was conducted in 5 infants, followed by a Phase II study with four sections (A-D). In the Phase II, sections A-D studies, time on infusion increased and younger gestational ages were included. RESULTS: IV infusion increased IGF-1 but with short half-life (0.5h) implying a need for continuous infusion. In order to obtain in utero levels of IGF-I, the dose was increased from 100 to 250 μg/kg/24 h and the infusion was prolonged from 3 weeks postnatal age until a postmenstrual age of 29 weeks and 6 days. CONCLUSION: The purpose has been to ensure high-quality research into the development of a new drug for preterm infants. We hope that our work will help to establish a new standard for the testing of medications for preterm infants.

Diplopia after cataract extraction is an unexpected outcome for the patient and often a source of confusion for the physician, owing to its relative infrequency. This article reviews the pertinent literature on the subject. Mechanisms include anesthetic myotoxicity, surgical trauma, optical aberrations, cortical disorders in patients with congenital strabismus, and the unmasking of previously unnoticed ocular misalignment. As the population continues to age and cataract extraction is performed in increasing volume, familiarity with this uncommon but important outcome may help to clarify and effectively treat post-cataract-extraction diplopia.

PURPOSE: To highlight the effect of ascent to high altitude on intraocular pressure (IOP) in a patient with primary open-angle glaucoma, who had previously undergone trabeculectomy in 1 eye. METHODS: Case report. RESULTS: A 66-year-old mountaineer with primary open-angle glaucoma and previous right trabeculectomy performed self-tonometry using a rebound tonometer (Icare HOME) before and during an expedition in the Himalaya. In the nonoperated eye, there was a statistically significant increase in IOP as the patient ascended to 5000 m over 8 days (R=0.790, P=0.001), consistent with recent literature. IOP increased by 1.73 mm Hg with each 1000 m increase in altitude. In the trabeculectomized eye there was no significant increase in IOP (R=0.219, P=0.172). CONCLUSIONS: Filtration surgery may be protective against IOP fluctuations associated with ascent to high altitude. Self-tonometry complements standard glaucoma care by providing opportunities for IOP monitoring outside office hours and in remote locations.

Corneal thickness is tightly regulated by its boundary endothelial and epithelial layers. The regulated set-point of corneal thickness likely shows inter-individual variations, changes by age, and response to stress. Using anterior segment-optical coherence tomography, we measure murine central corneal thickness and report on body size scaling of murine central corneal thickness during aging. For aged-matched mice, we find that corneal thickness depends on sex and strain. To shed mechanistic insights into these anatomical changes, we measure epithelial layer integrity and endothelial cell density during the life span of the mice using corneal fluorescein staining and in vivo confocal microscopy, respectively and compare their trends with that of the corneal thickness. Cornea thickness increases initially (1 month: 114.7 ± 3.0 μm, 6 months: 126.3 ± 1.6 μm), reaches a maximum (9 months: 129.3 ± 4.4 μm) and then reduces (12 months: 127 ± 2.9 μm, 13 months: 119.5 ± 7.6 μm, 14 months: 110.6 ± 10.6 μm), while the body size (weight) increases with age. We find that endothelial cell density reduces from 2 months old to 8 months old as the mice age and epithelial layer accumulates damages within this time frame. Finally, we compare murine corneal thickness with those of several other mammals including humans and show that corneal thickness has an allometric scaling with body size. Our results have relevance for organ size regulation, translational pharmacology, and veterinary medicine.

There are various treatments for cystoid macular edema (CME) secondary to retinitis pigmentosa (RP); however, the evidence for these treatments has not been previously systematically reviewed. Our review that includes 23 studies shows that oral carbonic anhydrase inhibitors (CAI) (including acetazolamide, methazolamide) and topical CAI (dorzolamide and brinzolamide) are effective first line treatments. In patients unresponsive to CAI treatment, intravitreal steroids (triamcinolone acetonide and sustained-release dexamethasone implant), oral corticosteroid (Deflazacort), intravitreal anti-vascular endothelial growth factor agents (ranibizumab and bevacizumab), grid laser photocoagulation, pars plana vitrectomy, or ketorolac were also effective in improving CME secondary to RP. Oral acetazolamide has the strongest clinical basis for treatment and was superior to topical dorzolamide. Rebound of CME was commonly seen in the long term, regardless of the choice of treatment. Oral acetazolamide should be the first line treatment in CME secondary to RP. Topical dorzolamide is an appropriate alternative in patients intolerant to adverse effects of oral acetazolamide. More studies are required to investigate the management of rebound CME.

Regulatory T cells (Tregs) are critical modulators of immune homeostasis. Tregs maintain peripheral tolerance to self-antigens, thereby preventing autoimmune disease. Furthermore, Tregs suppress excessive immune responses deleterious to the host. Recent research has deepened our understanding of how Tregs function at the ocular surface. This manuscript describes the classification, the immunosuppressive mechanisms, and the phenotypic plasticity of Tregs. We review the contribution of Tregs to ocular surface autoimmune disease, as well as the function of Tregs in allergy and infection at the ocular surface. Finally, we review the role of Tregs in promoting allotolerance in corneal transplantation.