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.

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.

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.

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.

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.

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.

Prevalence of Surgically Untreated Face, Head, and Neck Conditions in Uganda: A Cross-Sectional Nationwide Household Survey.

BACKGROUND: The Surgeons OverSeas Assessment of Surgical Need tool (SOSAS) was created to evaluate the burden of surgically treatable conditions in low- and middle-income countries. The goal of our study is to describe the face, head, and neck (FHN) conditions that need surgical care in Uganda, along with barriers to that care and disability from these conditions. METHODS: A 2-stage cluster randomized SOSAS survey was administered in a cross-sectional manner between August and September 2014. Participants included randomly selected persons in 105 enumeration areas in 74 districts throughout Uganda with 24 households in each cluster. The SOSAS survey collected demographic and clinical data on all respondents. Univariate and multivariate logistic models evaluated associations of demographic characteristics and clinical characteristics of the FHN conditions and outcomes of whether health care was sought or surgical care was received. RESULTS: Of the 4428 respondents, 331 (7.8%) reported having FHN conditions. The most common types of conditions were injury-related wounds. Of those who reported an FHN condition, 36% reported receiving no surgical care whereas 82.5% reported seeking health care. In the multivariate model, literacy and type of condition were significant predictors of seeking health care whereas village type, literacy, and type of condition remained significant predictors of receiving surgical care. CONCLUSIONS: Many individuals in Uganda are not receiving surgical care and barriers include costs, rural residency, and literacy. Our study highlights the need for targeted interventions in various parts of Uganda to increase human resources for surgery and expand surgical capacity.

Geospatial analysis of unmet pediatric surgical need in Uganda.

BACKGROUND: In low- and middle-income countries (LMICs), an estimated 85% of children do not have access to surgical care. The objective of the current study was to determine the geographic distribution of surgical conditions among children throughout Uganda. METHODS: Using the Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey, we enumerated 2176 children in 2315 households throughout Uganda. At the district level, we determined the spatial autocorrelation of surgical need with geographic access to surgical centers variable. FINDINGS: The highest average distance to a surgical center was found in the northern region at 14.97km (95% CI: 11.29km-16.89km). Younger children less than five years old had a higher prevalence of unmet surgical need in all four regions than their older counterparts. The spatial regression model showed that distance to surgical center and care availability were the main spatial predictors of unmet surgical need. INTERPRETATION: We found differences in unmet surgical need by region and age group of the children, which could serve as priority areas for focused interventions to alleviate the burden. Future studies could be conducted in the northern regions to develop targeted interventions aimed at increasing pediatric surgical care in the areas of most need. LEVEL OF EVIDENCE: Level III.

Epidemiology of pediatric surgical needs in low-income countries.

OBJECTIVE: According to recent estimates, at least 11% of the total global burden of disease is attributable to surgically-treatable diseases. In children, the burden is even more striking with up to 85% of children in low-income and middle-income countries (LMIC) having a surgically-treatable condition by age 15. Using population data from four countries, we estimated pediatric surgical needs amongst children residing in LMICs. METHODS: A cluster randomized cross-sectional countrywide household survey (Surgeons OverSeas Assessment of Surgical Need) was done in four countries (Rwanda, Sierra Leone, Nepal and Uganda) and included demographics, a verbal head to toe examination, and questions on access to care. Global estimates regarding surgical need among children were derived from combined data, accounting for country-level clustering. RESULTS: A total of 13,806 participants were surveyed and 6,361 (46.1%) were children (0-18 years of age) with median age of 8 (Interquartile range [IQR]: 4-13) years. Overall, 19% (1,181/6,361) of children had a surgical need and 62% (738/1,181) of these children had at least one unmet need. Based on these estimates, the number of children living with a surgical need in these four LMICs is estimated at 3.7 million (95% CI: 3.4, 4.0 million). The highest percentage of unmet surgical conditions included head, face, and neck conditions, followed by conditions in the extremities. Over a third of the untreated conditions were masses while the overwhelming majority of treated conditions in all countries were wounds or burns. CONCLUSION: Surgery has been elevated as an "indivisible, indispensable part of health care" in LMICs and the newly formed 2015 Sustainable Development Goals are noted as unachievable without the provision of surgical care. Given the large burden of pediatric surgical conditions in LMICs, scale-up of services for children is an essential component to improve pediatric health in LMICs.

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.

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.

Pilot study of a population-based survey to assess the prevalence of surgical conditions in Uganda.

BACKGROUND: Noncommunicable diseases, including those requiring surgical care, are increasingly straining low- and middle-income countries. Globally, 11% of all disability-adjusted life-years lost result from conditions requiring surgery; however, little is known about country-specific burden. We piloted a household-based survey in a periurban district of Uganda to estimate the prevalence of surgical conditions and to identify logistical challenges. METHODS: Our sample comprised 57 households in 5 enumeration areas in the Wakiso District, in central Uganda. Our survey tool was the Surgeons OverSeas Assessment of Surgical need. A household representative completed demographic and household death information, and 2 randomly selected household members completed questions on surgical conditions. RESULTS: Of 96 participants, 6 (6.3%; 95% CI, 2.3-13.1) had an existing, untreated surgical condition. The lifetime prevalence of surgical conditions was 26% (25/96). The most common barrier to access to care was lack of financial resources. Of the 3 deaths reported, 2 were associated with surgery. The mean household interview time was 36 minutes. The greatest challenge was efficient coordination with local team members and government officials. CONCLUSION: In this setting, the current prevalence of surgical conditions was nearly 1 in 10 persons, and lifetime occurrence was high, at 1 in 4 persons. Addressable challenges led to question revisions and a change in the data collection platform. A full-country study is both feasible and necessary to characterize the met and unmet need for surgical care 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.