Clinical applications of bioengineered tissue-cellular products for management of corneal diseases.

PURPOSE OF REVIEW: To discuss bioengineered tissue-cellular products for treatment of corneal diseases that are currently in clinical use. These include tissue-cellular products that have received regulatory approval, are being used off-label in clinical practice, or are in active use in clinical trials. RECENT FINDINGS: Due to the global shortage of donor corneal tissue, significant efforts have been made to develop bioengineering tissue-cellular products that can replace or augment the use of cadaveric tissue for corneal transplantation. The development of carrier substrates to support transplantation of cultivated limbal epithelial transplantation (CLET) has been a growing area of research. CLET offers a promising therapeutic alternative to conventional simple limbal epithelial transplantation and keratolimbal allografts for treatment of limbal stem cell deficiency. Engineered tissue matrices and porcine-derived corneas are potential alternatives to human donor tissue in anterior lamellar keratoplasty for corneal ulcers and scars, as well as intrastromal transplants for advanced keratoconus. For endothelial disease, substrate supported cultured endothelial cell grafts, and synthetic barrier devices are promising alternative to traditional endothelial keratoplasties. SUMMARY: There has been increasing interest in cellular and acellular bioengineered tissue-cellular and synthetic products for treatment of corneal diseases, and many of these products have already seen clinical use. Industry and academia have important roles in advancing these products to later phase clinical trials and comparing them to conventional allograft approaches. Future development of full thickness donor corneas with cultivated epithelium, endothelium, and stromal keratocytes in a biosynthetic matrix will likely be an important next step in tissue alternatives. Continued progress in this field will be critical for addressing the global disease burden from corneal blindness.

Downbeat nystagmus: a clinical review of diagnosis and management.

PURPOSE OF REVIEW: This review will extensively cover the clinical manifestations, causes, diagnostic evaluation, and management strategies of downbeat nystagmus (DBN). RECENT FINDINGS: Historically, MRI to assess for structural lesions at the cervicomedullary junction has been the primary diagnostic test in the evaluation of DBN since the 1980s. In recent years, there is increasing awareness of nonstructural causes of DBN including gluten ataxia, nutritional deficiencies, and paraneoplastic syndromes, among others. Medical management with aminopyridines has become first-line therapy in addition to disease-specific therapies. SUMMARY: DBN is a common form of acquired nystagmus and the differential diagnosis remains broad, including both benign and potentially fatal causes. For practical purposes, the causes can be categorized as structural vs. nonstructural with MRI as the ideal, initial diagnostic study to differentiate the two. General therapeutic options include pharmacotherapy to enhance Purkinje cell function, strabismus surgery or prisms to shift null points, and behavioural changes. Disease-specific treatment is necessarily broad, though a significant proportion of patients will be idiopathic.

Burden of Surgical Conditions in Uganda: A Cross-sectional Nationwide Household Survey.

OBJECTIVE: To quantify the burden of surgical conditions in Uganda. BACKGROUND: Data on the burden of disease have long served as a cornerstone to health policymaking, planning, and resource allocation. Population-based data are the gold standard, but no data on surgical burden at a national scale exist; therefore, we adapted the Surgeons OverSeas Assessment of Surgical Need survey and conducted a nation-wide, cross-sectional survey of Uganda to quantify the burden of surgically treatable conditions. METHODS: The 2-stage cluster sample included 105 enumeration areas, representing 74 districts and Kampala Capital City Authority. Enumeration occurred from August 20 to September 12, 2014. In each enumeration area, 24 households were randomly selected; the head of the household provided details regarding any household deaths within the previous 12 months. Two household members were randomly selected for a head-to-toe verbal interview to determine existing untreated and treated surgical conditions. RESULTS: In 2315 households, we surveyed 4248 individuals: 461 (10.6%) reported 1 or more conditions requiring at least surgical consultation [95% confidence interval (CI) 8.9%-12.4%]. The most frequent barrier to surgical care was the lack of financial resources for the direct cost of care. Of the 153 household deaths recalled, 53 deaths (34.2%; 95% CI 22.1%-46.3%) were associated with surgically treatable signs/symptoms. Shortage of time was the most frequently cited reason (25.8%) among the 11.6% household deaths that should have, but did not, receive surgical care (95% CI 6.4%-16.8%). CONCLUSIONS: Unmet surgical need is prevalent in Uganda. There is an urgent need to expand the surgical care delivery system starting with the district-level hospitals. Routine surgical data collection at both the health facility and household level should be implemented.

Geospatial Analysis of Unmet Surgical Need in Uganda: An Analysis of SOSAS Survey Data.

BACKGROUND: Globally, a staggering five billion people lack access to adequate surgical care. Sub-Saharan Africa represents one of the regions of greatest need. We sought to understand how geographic factors related to unmet surgical need (USN) in Uganda. METHODS: We performed a geographic information system analysis of a nationwide survey on surgical conditions performed in 105 enumeration areas (EAs) representing the national population. At the district level, we determined the spatial autocorrelation of the following study variables: prevalence of USN, hub distance (distance from EA to the nearest surgical center), area of coverage (geographic catchment area of each center), tertiary facility transport time (average respondent-reported travel time), and care availability (rate of hospital beds by population and by district). We then used local indicators of spatial association (LISA) and spatial regression to identify any significant clustering of these study variables among the districts. RESULTS: The survey enumerated 4248 individuals. The prevalence of USN varied from 2.0-45 %. The USN prevalence was highest in the Northern and Western Regions. Moran's I bivariate analysis indicated a positive correlation between USN and hub distance (p = 0.03), area of coverage (p = 0.02), and facility transport time (p = 0.03). These associations were consistent nationally. The LISA analysis showed a high degree of clustering among sets of districts in the Northern Sub-Region. CONCLUSIONS: This study demonstrates a statistically significant association between USN and the geographic variables examined. We have identified the Northern Sub-Region as the highest priority areas for financial investment to reduce this unmet surgical disease burden.

Quantifying the pediatric surgical need in Uganda: results of a nationwide cross-sectional, household survey.

PURPOSE: Little is known about the prevalence of pediatric surgical conditions in low- and middle-income countries. Many children never seek medical care, thus the true prevalence of surgical conditions in children in Uganda is unknown. The objective of this study was to determine the prevalence of surgical conditions in children in Uganda. METHODS: Using the Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey, we enumerated 4248 individuals in 2315 households in 105 randomly selected clusters throughout Uganda. Children aged 0-18 were included if randomly selected from the household; for those who could not answer for themselves, parents served as surrogates. RESULTS: Of 2176 children surveyed, 160 (7.4 %) reported a currently untreated surgical condition. Lifetime prevalence of surgical conditions was 14.0 % (305/2176). The predominant cause of surgical conditions was trauma (48.4 %), followed by wounds (19.7 %), acquired deformities (16.2 %), and burns (12.5 %). Of 90 pediatric household deaths, 31.1 % were associated with a surgically treatable proximate cause of death (28/90 deaths). CONCLUSION: Although some trauma-related surgical burden among children can be adequately addressed at district hospitals, the need for diagnostics, human resources, and curative services for more severe trauma cases, congenital deformities, and masses outweighs the current capacity of hospitals and trained pediatric surgeons in Uganda.

Estimation of Surgery Capacity in Haiti: Nationwide Survey of Hospitals.

BACKGROUND: Haiti's surgical capacity was significantly strained by the 2010 earthquake. As the government and its partners rebuild the health system, emergency and essential surgical care must be a priority. METHODS: A validated, facility-based assessment tool developed by WHO was completed by 45 hospitals nationwide. The hospitals were assessed for (1) infrastructure, (2) human resources, (3) surgical interventions and emergency care, and (4) material resources for resuscitation. Fisher's exact test was used to compare hospitals by sectors: public compared to private and mixed (public-private partnerships). RESULTS: The 45 hospitals included first-referral level to the national referral hospital: 20 were public sector and 25 were private or mixed sector. Blood banks (33% availability) and oxygen concentrators (58%) were notable infrastructural deficits. For human resources, 69% and 33% of hospitals employed at least one full-time surgeon and anaesthesiologist, respectively. Ninety-eight percent of hospitals reported capacity to perform resuscitation. General and obstetrical surgical interventions were relatively more available, for example 93% provided hernia repairs and 98% provided cesarean sections. More specialized interventions were at a deficit: cataract surgery (27%), cleft repairs (31%), clubfoot (42%), and open treatment of fractures (51%). CONCLUSION: Deficiencies in infrastructure and material resources were widespread and should be urgently addressed. Physician providers were mal-distributed relative to non-physician providers. Formal task-sharing to midlevel and general physician providers should be considered. The parity between public and private or mixed sector hospitals in availability of Ob/Gyn surgical interventions is evidence of concerted efforts to reduce maternal mortality. This ought to provide a roadmap for strengthening of surgical care capacity.

Surgeons OverSeas Assessment of Surgical Need (SOSAS) Uganda: Update for Household Survey.

INTRODUCTION: The first step in improving surgical care delivery in low- and middle-income countries (LMICs) is quantifying surgical need. The Surgeons OverSeas Assessment of Surgical Need (SOSAS) is a validated household survey that has been previously implemented in three LMICs with great success. We implemented the SOSAS survey in Uganda, a medium-sized country with comparatively more language and ethnic group diversity. METHODS: The investigators partnered with the Performance Monitoring and Accountability 2020 (PMA2020) Uganda to access a data collection platform sampling 2520 households in 105 randomly selected enumeration areas. Due to geographic size consideration and language diversity, SOSAS's methodology was updated in three significant dimensions (1) technology, (2) staff management, and (3) questionnaire adaptations. RESULTS: The SOSAS survey was successfully implemented with non-medically trained but field proven research assistants. We sampled 2315 of 2402 eligible households (response rate 96.4 %) and 4248 of 4374 eligible individual respondents (response rate 97.1 %). The female-to-male ratio was 51.1-48.9 %. Total survey cost was USD 73,145 and data collection occurred in 14 days. DISCUSSION: SOSAS Uganda has demonstrated that non-medically trained, but university-educated, experienced researchers supervised by academic surgeons can successfully perform accurate data collection of SOSAS. SOSAS can be successfully implemented within larger and more diverse LMICs using existing national survey platforms, and SOSAS Uganda provides insights on how SOSAS can be executed specifically within other PMA2020 program countries.

Topical Tacrolimus Compared With Oral Tacrolimus for Postoperative Immunosuppression in Primary Keratolimbal Allograft.

PURPOSE: The aim of this study was to compare outcomes between topical tacrolimus and oral tacrolimus as the primary calcineurin inhibitor for postoperative immunosuppression after primary keratolimbal allograft (KLAL) transplantation for limbal stem cell deficiency (LSCD). METHODS: We performed a retrospective, comparative cohort study at a single tertiary referral center (University of MN) of all patients who underwent primary KLAL between 2014 and 2021. Eyes were grouped into those which received topical tacrolimus as the only calcineurin inhibitor (topical group) and eyes in which patients received oral tacrolimus with or without topical tacrolimus (oral group). Clinical and donor tissue data were obtained and compared between the 2 groups. RESULTS: In total, 27 eyes of 22 patients (median age 42 years, range 20-79 years) were included, of which 18 eyes were in the oral group and 9 eyes were in the topical group. The mean follow-up time was 33.2 ± 22.6 months. The most frequent etiology of LSCD was alkaline burn (33.3%). At 36 months, graft failure occurred in 6 eyes in the oral group (33.3%) and 2 eyes in the topical group (22.1%) ( P = 0.57). The failure rate in the oral group was 9.1 per 1000 person-months versus 8.4 per 1000 person-months in the topical group ( P = 0.96). The median improvement in BCVA was logMAR -0.975 and logMAR -0.45 for the oral and topical group, respectively ( P = 0.50). CONCLUSIONS: With careful patient selection, topical tacrolimus may be a viable alternative to oral tacrolimus in KLAL.

Descemet Stripping Endothelial Keratoplasty in Patients With a Custom Foldable Silicone Artificial Iris: Safety and Efficacy Outcomes.

PURPOSE: To assess outcomes of Descemet stripping endothelial keratoplasty (DSEK) in eyes with custom artificial iris (CAI) implantation. METHODS: This is a retrospective, interventional, consecutive, surgical case series of patients who underwent DSEK after CAI implantation between 2010 and 2021 at 2 referral centers. Primary safety measures were loss of corrected distance visual acuity (CDVA), increase in intraocular pressure (IOP), development or progression of glaucoma, and intraoperative and postoperative complications. Efficacy measures were graft survival at year 1 and improvement in cosmesis at postoperative month 3. In general, measures were compared between baseline and postoperative year 1 while any complication was reported for the full follow-up period. RESULTS: Thirty-nine eyes of 39 patients were identified. 64.1% of eyes had acquired aniridia from trauma. The mean follow-up interval was 27.7 months (range 12.2-117.4). Median CDVA improved from logMAR 1.0 to 0.7 at year 1 (P = 0.0047). At the final follow-up, permanent loss of CDVA occurred in 25.6% of eyes, of which 90% was due to glaucoma. The most common postoperative complication was IOP elevation (66.7% of eyes). Graft survival at postoperative year 1 was 82.0% (95% confidence interval, 66.3-91.4). Secondary graft failure occurred in 28.2% of eyes at a mean duration of 39.7 months (SD 27.9 months) after DSEK. Cosmesis improved among 87.2% of eyes at postoperative month 3. CONCLUSIONS: DSEK is an effective procedure for addressing corneal edema in eyes with a CAI, but a majority develop elevated IOP and graft survival is shorter than in eyes without a CAI.

Update on Femtosecond Laser-Enabled Keratoplasty.

ABSTRACT: The application of femtosecond lasers to corneal transplantation is an intriguing proposition with many potential benefits to patients with various corneal diseases. The customized trephination pattern for donor and host matching offers many advantages regarding wound integrity and high precision of donor and recipient match at the interface, which should lead to faster healing and visual rehabilitation. Femtosecond laser-enabled keratoplasty (FLEK) is an advancement of conventional trephination penetrating keratoplasty, and in large clinical cohorts to date, there are meaningful improvements in visual outcomes and a lower risk of graft rejection. Femtosecond laser-enabled deep anterior lamellar keratoplasty (Femto-DALK) combines the advantage of a customized trephination pattern with the deep anterior lamellar keratoplasty procedure, which eliminates the risk of endothelial rejection. Furthermore, the precision of the femtosecond laser may offer additional novel approaches to lamellar keratoplasties. In time, advancements in femtosecond laser platforms will help cornea surgeons realize the added benefits and better optimize outcomes for patients, such that the cost-benefit calculus shifts toward wider accessibility for patients. Prospective randomized-controlled trials are needed to definitively determine the impact of femtosecond laser-enabled keratoplasties on long-term outcomes.

Teaching Smartphone Funduscopy with 20 Diopter Lens in Undergraduate Medical Education.

PURPOSE: To assess attitudes of pre-clinical undergraduate medical students toward learning smartphone funduscopy (SF) and its appropriateness as a teaching tool. PATIENTS AND METHODS: Second year medical students received instruction on direct ophthalmoscopy (DO) and SF; they were then paired with a peer and randomly assigned to perform DO or SF first. The SF technique involved freehand alignment of the axes of the smartphone camera with a condenser lens. Both techniques were done through a maximally dilated pupil. A questionnaire was completed to acquire data on baseline experience, performance of both examination techniques, attitudes, and appropriateness. Statistical significance testing and Bland-Altman analysis were used to determine differences between DO and SF, and a multivariable mixed regression model was fitted to identify any predictors for positive attitudes toward DO or SF. RESULTS: One hundred thirty-seven (137) individuals completed the study. A similar proportion of students could identify the optic nerve, macula, and vessels using DO and SF. However, self-reported quality scores were higher for DO for the optic nerve (p = 0.006) and macula (p = 0.08). The mean (standard deviation) attempts to identify these major structures were 2.7 (SD 2.3) for DO and 4.5 (SD 2.9) for SF (p < 0.001). Attitudes of students were consistently more positive toward DO across the five questions assessed. A small subset of students had equally positive attitudes toward DO and SF. Improved quality scores were predictive of positive attitudes for both DO and SF. Ultimately, 24% of students preferred SF over DO. CONCLUSION: Among inexperienced examiners of the fundus through a dilated pupil, SF is a non-inferior technique to DO in identifying structures. Despite overall favorable attitudes towards the more familiar DO, those students who quickly learned the SF technique had similar satisfaction scores. Teaching SF should be considered in undergraduate medical education.

Smartphone-based Ophthalmic Imaging Compared With Spectral-domain Optical Coherence Tomography Assessment of Vertical Cup-to-disc Ratio Among Adults in Southwestern Uganda.

PRECIS: Using optical coherence tomography (OCT) measurements as a reference standard for vertical cup-to-disc ratio (vCDR), a smartphone-based ophthalmic camera has a sensitivity of 67.7% and specificity of 96.7% to detect a vCDR>0.5. PURPOSE: The purpose of this study was to assess the performance of a smartphone-based ophthalmic camera system using an Apple iPhone 6S and an adapter, Paxos Scope, to obtain adequate dilated fundus photos to measure clinically useful vCDR cutoffs. PATIENTS AND METHODS: Adult patients from a government tertiary level eye hospital in Southwestern Uganda were prospectively recruited from January to April 2019. All patients experienced a comprehensive eye examination, dilated posterior segment indirect ophthalmoscope imaging with the Paxos Scope, and spectral-domain OCT imaging with a Cirrus HD-OCT to measure vCDR. Patients' eyes excluded had media opacities or existing disease precluding a view of the fundus. Fundus images underwent a single masked review to assign vCDR at increments of 0.1. Descriptive statistics, parametric and χ2 tests for significance, repeated measures correlation, κ, receiver operating characteristics curve, and Bland-Altman were used to assess the data. RESULTS: Among 467 (consecutive) individuals, fundus photographs acquired with the Paxos Scope demonstrated a 67.7% [95% confidence interval (CI), 63.0-72.0] sensitivity and 96.7% (95% CI, 94.2-98.3) specificity to detect a vCDR>0.5, using OCT as the reference standard. A total of 138 eyes were excluded due to poor imaging acquisition, such as dense cataract, rendering 796 eyes for analysis. The vCDR from graded Paxos Scope images and OCT correlated well with repeated measures correlation of 0.82 (95% CI, 0.77-0.86, P<0.001) and agreement, dichotomized as >0.5 or ≤0.5, was 80.9% (κ=0.63±0.034, P<0.001). Among glaucoma and glaucoma suspects (85 eyes), the sensitivity and specificity dichotomized using vCDR>0.5 were 97.5% (95% CI, 91.3-99.7) and 80.0% (95% CI, 28.4-99.5), respectively. The area under the receiver operating characteristics curve was 0.92 (95% CI, 0.89-0.94) for all eyes and 0.98 (95% CI, 0.78-1.0) for glaucoma and glaucoma suspects. CONCLUSIONS: The Paxos Scope produced images that can be reliably used to estimate vCDR, which is closely aligned with the automated algorithm from the OCT optic disc cube scan. The low-cost, ready-to-integrate adapter, and minimal training requirements make it a viable option for population-based screening in low-resource settings.

Cancer-Associated Retinopathy due to Clear Cell Renal Carcinoma.

An 84-year-old female presented with bilateral scotomas and progressive nyctalopia over 1 year. Best-corrected visual acuity was 20/50 in both eyes with reduced color vision. Goldmann visual field showed bilateral cecocentral scotomas and generalized constriction of the visual fields. This led to an electroretinogram showing an electronegative pattern consistent with autoimmune retinopathies. Infectious workup was negative. Anti-retinal antibodies were positive, leading to a presumed diagnosis of cancer-associated retinopathy (CAR). Imaging showed a previously unknown left renal lower pole mass, and she underwent a radical nephrectomy. Biopsy showed nuclear grade-3 clear cell renal carcinoma staged T1. The patient was treated with oral prednisone with no ocular improvement. We report on a rare case of clear cell renal carcinoma causing CAR. CAR is an important paraneoplastic syndrome to diagnose since the majority of ocular cases precede other manifestations of malignancy. Therefore, a timely diagnosis of CAR can be lifesaving or at least life-extending.

Presumed mast cell choroidal infiltrate in aggressive systemic mastocytosis.

PURPOSE: To report a rare case of a unilateral choroidal mast cell infiltration in a patient with aggressive systemic mastocytosis (ASM). OBSERVATIONS: The patient is a man in his fifties with a diagnosis of ASM. He developed visual complaints in the right eye associated with an area of subretinal fluid on fundus examination. Visual acuity at presentation was 20/150 in the right eye and 20/25 in the left eye. After ophthalmic and radiologic imaging workup, the patient was diagnosed with presumed choroidal mast cell infiltrate. The index of suspicion was high due to the prior ASM diagnosis. External beam radiation and intravitreal injection treatments were offered but the patient declined. The patient was switched from interferon to a new targeted systemic therapy for ASM, midostaurin. Despite some mixed, temporary response in systemic symptoms/signs of ASM at four months, the choroidal lesion and subretinal fluid were stable with visual acuity at 20/125. CONCLUSION AND IMPORTANCE: Mast cell choroidal infiltration in ASM should be considered as part of the differential with acute/subacute vision changes. Diagnosis requires exclusion of other possibilities with ocular imaging and in this case, monitoring for development of other malignancies in which there were none. Midostaurin's ocular response was not on par with systemic response. Additional localized ocular therapies may be required.

Corneal Blindness in Asia: A Systematic Review and Meta-Analysis to Identify Challenges and Opportunities.

PURPOSE: To describe the causes and prevalence of moderate-to-severe visual impairment (MSVI) and blindness from corneal diseases, as well as corneal transplantation across Asia. METHODS: A meta-analysis of the published literature to identify population-based surveys conducted from 2008 to 2019 in 22 Asian countries regarding the prevalence and causes of MSVI and blindness from corneal disease, and a review of national corneal transplant data and eye bank statistics. RESULTS: A total of 5307 records were screened to identify 57 reports that were used to estimate a prevalence of MSVI and blindness caused by corneal diseases in Asia of 0.38% (95% confidence interval, 0.29%-0.48%). The most frequent corneal diseases were infectious keratitis, trauma, and pseudophakic bullous keratopathy. As expected, these represented the most common indications for corneal transplantation, although the percentages in each country differed based on the level of economic development, with pseudophakic bullous keratopathy being the most common indication in countries with higher gross national income per capita. Despite this, endothelial keratoplasty is not the most commonly performed form of corneal transplantation in any Asian country and represents only a small percentage of keratoplasty procedures performed in most countries. CONCLUSIONS: The prevalence of MSVI and blindness from corneal disease in Asia is approximately 0.4%, with a nearly 20-fold difference in the national prevalence across the region. The indications for keratoplasty, reflective of the causes of corneal dysfunction, also vary, more so according to the gross national income than to geographic location, and only a few Asian countries have rates of corneal transplantation above international means.

Clinical Characteristics of a Case Series of Ocular Syphilis With 3 Cases Requiring Multiple Vitrectomies After Late Diagnosis.

Purpose: This work describes the characteristics and unique features of ocular syphilis. Methods: Ten serologically proven cases of ocular syphilis were retrospectively analyzed. Results: Eighteen eyes of 10 patients were affected. Nine of 10 patients were male and the mean age was 58 years (range, 36-81 years). HIV antibody testing was positive in 3 patients (30%). Five cases were first diagnosed by an ophthalmologist. One patient presented with a syphilitic rash. The most common ocular findings were panuveitis (n = 6) and cystoid macular edema (n = 4). Ocular involvement was unilateral in 2 cases and bilateral in 8. Best-corrected visual acuity improved in 13 of 18 eyes (72%) after treatment. Three cases developed recurrent retinal detachments that required repair with silicone oil. Conclusions: Most cases were HIV negative. Syphilitic uveitis can be the initial presentation of syphilis without classic systemic manifestation. Ophthalmologists play an important role in the diagnosis and treatment of syphilis.

Quantitative Fundus Autofluorescence in Rhesus Macaques in Aging and Age-Related Drusen.

Purpose: To employ quantitative fundus autofluorescence (qAF) imaging in rhesus macaques to noninvasively assess retinal pigment epithelial (RPE) lipofuscin in nonhuman primates (NHPs) as a model of aging and age-related macular degeneration (AMD). Methods: The qAF imaging was performed on eyes of 26 rhesus macaques (mean age 18.8 ± 8.2 years, range 4-27 years) with normal-appearing fundus or with age-related soft drusen using a confocal scanning laser ophthalmoscope with 488 nm excitation and an internal fluorescence reference. Eyes with soft drusen also underwent spectral-domain optical coherence tomography imaging to measure drusen volume and height of individual drusen lesions. The qAF levels were measured from the perifoveal annular ring (quantitative autofluorescence 8 [qAF8]) using the Delori grid, as well as focally over individual drusen lesions in this region. The association between qAF levels and age, sex, and drusen presence and volume were determined using multivariable regression analysis. Results: Mean qAF levels increased with age (P < 0.001) and were higher in females (P = 0.047). Eyes with soft drusen exhibited reduced mean qAF compared with age-matched normal eyes (P = 0.003), with greater drusen volume showing a trend toward decreased qAF levels. However, qAF levels are focally increased over most individual drusen (P < 0.001), with larger drusen appearing more hyperautofluorescent (R2 = 0.391, P < 0.001). Conclusions: In rhesus macaques, qAF levels are increased with age and female sex, but decreased in eyes with soft drusen, similar to human AMD. However, drusen lesions appear hyperautofluorescent unlike those in humans, suggesting similarities and differences in RPE lipofuscin between humans and NHPs that may provide insight into drusen biogenesis and AMD pathogenesis.

Diagnosis and Management of Trochleodynia, Trochleitis, and Trochlear Headache.

Migraine and tension-type headaches (TTHs) comprise a significant burden of neurological disease globally. Trochleodynia, also known as primary trochlear headache or trochleitis, may go unrecognized and contribute to worsening of these headache disorders. It may also present in isolation. We review the English literature on this under-recognized condition and describe what is known about the theorized pathophysiology, clinical presentation, and differential diagnosis. We also present a management algorithm for patients presenting with trochleodynia.

Optimizing Care for Ugandans with Untreated Abdominal Surgical Conditions.

BACKGROUND: Abdominal operations account for a majority of surgical volume in low-income countries, yet population-level prevalence data on surgically treatable abdominal conditions are scarce. OBJECTIVE: In this study, our objective was to quantify the burden of surgically treatable abdominal conditions in Uganda. METHODS: In 2014, we administered a two-stage cluster-randomized Surgeons OverSeas Assessment of Surgical Need survey to 4,248 individuals in 105 randomly selected clusters (representing the national population of Uganda). FINDINGS: Of the 4,248 respondents, 185 reported at least one surgically treatable abdominal condition in their lifetime, giving an estimated lifetime prevalence of 3.7% (95% CI: 3.0 to 4.6%). Of those 185 respondents, 76 reported an untreated condition, giving an untreated prevalence of 1.7% (95% CI: 1.3 to 2.3%). Obstructed labor (52.9%) accounted for most of the 238 abdominal conditions reported and was untreated in only 5.6% of reported conditions. In contrast, 73.3% of reported abdominal masses were untreated. CONCLUSIONS: Individuals in Uganda with nonobstetric abdominal surgical conditions are disproportionately undertreated. Major health system investments in obstetric surgical capacity have been beneficial, but our data suggest that further investments should aim at matching overall surgical care capacity with surgical need, rather than focusing on a single operation for obstructed labor.

Surgical need among the ageing population of Uganda.

BACKGROUND: Uganda's ageing population (age 50 years and older) will nearly double from 2015 to 2050. HIV/AIDS, diabetes, stroke among other disease processes have been studied in the elderly population. However, the burden of disease from surgically-treatable conditions is unknown. OBJECTIVES: To determine the proportion of adults above 50 years with unmet surgical need and deaths attributable to probable surgically-treatable conditions. METHODS: A cluster randomized sample representing the national population of Uganda was enumerated. The previously validated Surgeons Overseas assessment of surgical need instrument, a head-to-toe verbal interview, was used to determine any surgically-treatable conditions in two randomly-selected living household members. Deaths were detailed by heads of households. Weighted metrics are calculated taking sampling design into consideration and Taylor series linearization was used for sampling error estimation. RESULTS: The study enumerated 425 individuals above age 50 years. The prevalence proportion of unmet surgical need was 27.8% (95%CI, 22.1-34.3). This extrapolates to 694,722 (95%CI, 552,279-857,157) individuals living with one or more surgically treatable conditions. The North sub-region was observed to have the highest prevalence proportion. Nearly two out of five household deaths (37.9%) were attributed to probable surgically treatable causes. CONCLUSION: There is disproportionately high need for surgical care among the ageing population of Uganda with approximately 700,000 consultations needed.