Three-year outcomes of de novo tacrolimus extended-release tablets (LCPT) compared to twice-daily tacrolimus in adult heart transplantation.

BACKGROUND: Extended-release tacrolimus for prophylaxis of allograft rejection in heart transplant (HT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release (IR-) tacrolimus. We compared long-term efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. METHODS: 25 prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 3 years following transplant was compared between groups using non-inferiority analysis. RESULTS: LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 16% (90%CI, -37%, -1%, non-inferiority p = 0.002) up to 3 years following heart transplant. Up to 3-years post-transplant, 14 patients remained on once-daily LCPT and 10 patients were switched to IR-tacrolimus due to lack of insurance coverage. There were no significant differences in the rate of chronic kidney disease requiring dialysis, cytomegalovirus requiring treatment, cardiac allograft vasculopathy, and malignancy within 3 years following transplant. CONCLUSION: LCPT is non-inferior in efficacy to IR-tacrolimus in heart transplantation with a similar safety profile. Narrowly-constrained FDA labels specific to kidney transplant remain a barrier to consistent access to many immunosuppressant medications for recipients of non-kidney solid organs. We recommend the FDA consider developing facile pathways for expanding the approved label of extended-release tacrolimus formulations to heart transplant recipients.

Early elevated donor-derived cell-free DNA levels in heart transplant recipients following precision-controlled cardiac transport system or ice-cooled organ transport.

BACKGROUND: Recent innovations in temperature-controlled cardiac transportation allow for static hypothermic preservation of transplant organs during transportation. We assessed differences in donor-derived cell-free DNA (dd-cfDNA) using the SherpaPak cardiac transport system (SCTS) and traditional ice transportation. METHODS: Single-organ heart transplant recipients between January 2020 and January 2022 were included if they had dd-cfDNA measures ≤6 weeks post-transplant along with the baseline biopsy at 6 weeks as part of the surveillance protocol and no biopsy-confirmed rejection ≤90 days. Elevated dd-cfDNA ≥.20% were compared between groups using logistic regression including a subject effect. RESULTS: Of 65 hearts transplanted, 30 were transported with SCTS and 35 on ice. Recipient characteristics were similar between groups. Donors in the SCTS group were older (34 vs. 40 years, p = .04) with a longer total ischemic time (171 vs. 212 min, p = .002). Recipients in the SCTS group had a greater risk of elevated dd-cfDNA unadjusted and adjusted for donor age, and prolonged ischemic times > 3.5 h (Unadjusted odds ratio: 4.9, 95%-CI: 1.08-22.5, p = .039 and Adjusted odds ratio: 5.5, 95%-CI: 1.03-29.6, p = .046). Primary graft dysfunction rates and 1-year mortality were comparable between groups. CONCLUSION: Elevated dd-cfDNA in patients procured with SCTS may indicate that graft injury was not negated relative to ice transport. However, there were no clinical differences noted in short or long-term outcomes including mortality despite a longer ischemic time in the SCTS group.

Heart transplant Recipients' perspectives on invasive versus Non-invasive graft failure surveillance Methods.

BACKGROUND: Heart transplant recipients must regularly be assessed for graft rejection; however, endomyocardial biopsy (EMB), can be stressful, painful, and inconvenient. AlloMap® is the only commercially available non-invasive test for graft rejection. Current guidelines include AlloMap® testing in low-risk patients OBJECTIVES: To examine the patients' perspective, this study compared patients' experiences of AlloMap® and EMB surveillance at our center. METHODS: We enrolled consecutive heart transplant recipients who were to undergo routine EMB and AlloMap® testing (on different visits) to quantify their anxiety on the GAD-7 scale and their pain level on the Polyclinic Pain Scale. We assessed paired differences of anxiety and pain within patients according to surveillance method. RESULTS: We studied 43 participants (median age 60.5[54, 66] years; 35(81%) men; 27(63%) Caucasian). The median GAD-7 scores were 1[0, 4] and 2[0, 5] prior to EMB and AlloMap®, respectively (paired difference: 0[-1, 1],P = 0.323). The median pain scores were 1[0, 1] and 0[0, 0] for EMB and AlloMap®, respectively. Patients experienced less pain with AlloMap® testing compared to EMB (EMB-AlloMap;1[0, 1],P = 0.006). Seven (16%) participants experienced a total of 9 adverse events (pain, bruising, bleeding, swelling) from EMB vs 2(5%) participants who experienced a total of 3 adverse events (pain, bruising) from AlloMap®(P = 0.059). CONCLUSION: Heart transplant recipients had less pain and fewer adverse events while undergoing graft rejection surveillance with AlloMap® testing compared to EMB. An additional benefit of AlloMap® testing is that it may be performed at home and reduce these high-risk patients' infectious exposures.

Liver stiffness and prediction of cardiac outcomes in patients with acute decompensated heart failure.

BACKGROUND: In acute decompensated heart failure (ADHF), noninvasive markers that predict morbidity and mortality are limited. Liver stiffness measurement (LSM) increases with hepatic fibrosis; however, it may be falsely elevated in patients with ADHF in the absence of liver disease. We investigated whether elevated LSM predicts cardiac outcomes in ADHF. METHODS: In a prospective study, we examined 52 ADHF patients without liver disease between 2016 and 2017. Patients underwent liver 2D shear wave elastography (SWE) and were followed for 12 months to assess the outcomes of left ventricular assist device (LVAD), heart transplant (HT) or death. RESULTS: The median LSM was elevated in patients who received an LVAD or HT within 30-days compared to those who did not (median [IQR]: 55.6 [22.5 - 63.4] vs 13.8 [9.5 - 40.3] kPa, p = .049). Moreover, the risk of composite outcome was highest in the 3rd tertile (> 39.8 kPa compared to 1st and 2nd combined, HR 2.83, 95% CI 1.20- 6.67, p = .02). Each 1-kPa increase in LSM was associated with a 1%-increase in the incidence rate of readmissions (IRR 1.01, 95% CI 1.00-1.02, p = .01). CONCLUSIONS: LSM may serve as a novel noninvasive tool to determine LVAD, HT, or death in patients with ADHF.

Urinary Cell-Cycle Arrest Biomarkers as Early Predictors of Acute Kidney Injury After Ventricular Assist Device Implantation or Cardiac Transplantation.

OBJECTIVES: Acute kidney injury (AKI) remains a leading source of morbidity and mortality after cardiothoracic surgery. Insulin-like growth factor-binding protein 7 (IGFBP7), and tissue inhibitor of metalloproteinases-2 (TIMP-2), are novel early-phase renal biomarkers that have been validated as sensitive predictors of AKI. Here the authors studied the efficacy of these biomarkers for predicting AKI after left ventricular assist device (LVAD) implantation and cardiac transplantation. DESIGN/SETTING/PARTICIPANTS/INTERVENTIONS: This was a prospective study of 73 patients undergoing LVAD implantation (n = 37) or heart transplant (n = 36) from 2016 to 2017 at the authors' center. TIMP-2 and IGFBP7 were measured with the NephroCheck Test on urine samples before surgery and one-to-six hours after surgery. NephroCheck scores were assessed as predictors of moderate/severe AKI (Kidney Disease International Global Outcomes 2/3 creatinine criteria) within 48 hours of surgery, and the association with survival to one year was investigated. MEASUREMENTS AND MAIN RESULTS: The LVAD and transplant cohorts overall were similar in demographics and baseline creatinine (p > 0.05), with the exception of having more African-American patients in the LVAD arm (p = 0.003). Eleven (30%) LVAD and 16 (44%) transplant patients developed moderate/severe AKI. Overall, AKI was associated with postsurgery NephroCheck (odds ratio [95% confidence interval] for 0.1 mg/dL increase: 1.36 [1.04-1.79]; p = 0.03), but not with baseline NephroCheck (p = 0.92). When analyzed by cohort, this effect remained for LVAD (1.68 [1.05-2.71]; p = 0.03) but not for transplant (p = 0.15). Receiver operating characteristic analysis showed postoperative NephroCheck to be superior to baseline creatinine in LVAD (p = 0.046). Furthermore, an increase of 0.1 mg/dL in postoperative NephroCheck was associated with a 10% increase in the risk of mortality (adjusted hazard ratio: 1.11 [1.01-1.21]; p = 0.04) independent of age and body mass index. CONCLUSION: Assessment of TIMP-2 and IGFBP7 within six hours after surgery appeared effective at predicting AKI in patients with LVADs. Larger studies are warranted to validate these findings.

Impact of antimicrobial selection for prophylaxis of left ventricular assist device surgical infections.

BACKGROUND: Surgical site infections (SSIs) after left ventricular assist device (LVAD) implantation are associated with high mortality, while surgical prophylaxis is variable. METHODS: This retrospective study included adult patients who underwent LVAD implantation at a single center. We compared outcomes in patients who received narrow antimicrobial prophylaxis (cefazolin, vancomycin, or both) to those who received broad antimicrobial prophylaxis (any antimicrobial combination targeting gram-positive and gram-negative organisms not included in the narrow group) at 30-day and 1-year postimplantation. Cox-proportional hazards models and log-rank tests were used for survival analysis. RESULTS: Among the 39 and 65 patients comprising narrow and broad groups respectively, there was no difference in rate of SSI at 30 days (6.2% vs. 12.8%, p = .290) and 1 year (16.9% vs. 25.6%, p = .435). Comparing narrow to broad prophylaxis, the risk of mortality (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.15-1.35, logrank p = .14), and composite of mortality and infection was reduced (HR = 0.92, 95% CI = 0.45-1.88, logrank p = .83), but did not reach statistical significance. Most culture positive infections were due to gram-positive bacteria (70%) and the most common organisms were the Staphylococcus spp (47%). There were no significant differences in the rate of SSI at 1-year (p = 1.00) and mortality (p = .33) by device type. CONCLUSIONS: The rates of infection and all-cause mortality were not different between patients who received narrow or broad prophylaxis. This highlights an opportunity for institutions to narrow their surgical infection prophylaxis protocols to primarily cover gram-positive organisms.

Trends in post-heart transplant biopsies for graft rejection versus nonrejection.

With alternatives such as gene profiling available for surveillance after orthotopic heart transplantation, we sought to evaluate the utilization of endomyocardial biopsies (EMBs) for hospitalized patients after heart transplantation. Surveillance EMBs in patients with and without complications were evaluated from the 2004 to 2014 National Inpatient Sample. Over the study period, there was no significant change in the number of EMB procedures performed (P = 0.44). Of 37,955 EMBs, 2283 (6%) were in the setting of graft complications, while 35,672 EMBs were not related to graft complications. EMBs in graft complications did not show a significant increase in length of stay over time (P = 0.06), but had a significant increase in cost over time (P = 0.001). However, those with graft complications had an average of a 5-day longer length of stay (P < 0.001) and costs that were $88,816 (P < 0.001) more expensive compared with those without graft complications. In conclusion, the vast majority of in-hospital EMBs were not related to heart transplantation complications. Nevertheless, EMB hospitalizations with graft complications showed significantly greater length of stay and cost. With the COVID-19 pandemic, it seems more effective to use minimal-contact health surveillance methods rather than invasive EMBs.

Morphological Differences in the Inferior Oblique Muscles from Subjects with Over-elevation in Adduction.

Purpose: We examined inferior oblique muscles from subjects with over-elevation in adduction for characteristics that might shed light on the potential mechanisms for their abnormal eye position. Methods: The inferior oblique muscles were obtained at the time of surgery in subjects diagnosed with either primary inferior oblique overaction or Apert syndrome. The muscles were frozen and processed for morphometric analysis of myofiber size, central nucleation, myosin heavy chain (MyHC) isoform expression, nerve density, and numbers of neuromuscular junctions per muscle section. Results: The inferior oblique muscles from subjects with Apert Syndrome were smaller, and had a much more heterogeneous profile relative to myofiber cross-sectional area compared to controls. Increased central nucleation in the Apert syndrome muscles suggested on-going myofiber regeneration or reinnervation over time. Complex changes were seen in the MyHC isoform patterns that would predict slower and more sustained contractions than in the control muscles. Nerve fiber densities were significantly increased compared to controls for the muscles with primary inferior oblique overaction and Apert syndrome that had no prior surgery. The muscles from Apert syndrome subjects as well as those with primary inferior oblique overaction with no prior surgery had significantly elevated numbers of neuromuscular junctions relative to the whole muscle area. Conclusions: The muscles from both sets of subjects were significantly different from control muscles in a number of properties examined. These data support the view that despite similar manifestations of eye misalignment, the potential mechanism behind the strabismus in these subjects is significantly different.

Outcomes of Moderate-to-Severe Acute Kidney Injury following Left Ventricular Assist Device Implantation.

BACKGROUND: Although acute kidney injury (AKI) is a common complication following cardiac surgery, less is known about the occurrence and consequences of moderate/severe AKI following left ventricular assist device (LVAD) implantation. METHODS: All patients who had an LVAD implanted at our center from 2008 to 2016 were reviewed to determine the incidence of, and risk factors for, moderate/severe (stage 2/3) AKI and to compare postoperative complications and mortality rates between those with and those without moderate/severe AKI. RESULTS: Of 246 patients, 68 (28%) developed moderate/severe AKI. A multivariable logistic regression comprising body mass index and prior sternotomy had fair predictive ability (area under the curve = 0.71). A 1-unit increase in body mass index increased the risk of moderate/severe AKI by 7% (odds ratio = 1.07; 95% confidence interval: 1.03-1.11); a prior sternotomy increased the risk more than 3-fold (odds ratio = 3.4; 95% confidence interval: 1.84-6.43). The group of patients with moderate/severe AKI had higher rates of respiratory failure and death than the group of patients with mild/no AKI. Patients with moderate/severe AKI were at 3.2 (95% confidence interval: 1.2-8.2) times the risk of 30-day mortality compared to those without. Even after adjusting for age and Interagency Registry for Mechanically Assisted Circulatory Support profile, those with moderate/severe AKI had 1.75 (95% confidence interval: 1.03-3.0) times the risk of 1-year mortality compared to those without. DISCUSSION: Risk-stratifying patients prior to LVAD placement in regard to AKI development may be a step toward improving surgical outcomes.

Anxiety, depression, and healthcare utilization 1 year after cardiac surgery.

BACKGROUND: While it is known that depression and anxiety influence cardiac surgery recovery, the mechanisms of such remain unclear. We examined the influence of anxiety and/or depression on health care utilization and quality of life (QOL) in the 12 months following cardiac surgery. METHODS: (N = 306) patients at two North Texas hospitals were assessed pre-operatively, at 30 days, and one year post-operatively using the Hospital Anxiety and Depression Scale and Kansas City Cardiomyopathy Quality of Life measures. Patient healthcare utilization metrics included length of stay, outpatient visits, hospital stays, emergency department (ED) visits, and home healthcare. RESULTS: At 12 months post-surgery, anxious patients sustained more outpatient visits (p = 0.0129) than those without anxiety. Depressed patients differed significantly from non-depressed patients with significantly lower QOL (p < 0.01), as well as more readmissions, ED visits, home healthcare use, and a longer length of stay (all p < 0.05). CONCLUSIONS: Depressed patients utilized more expensive healthcare services and had lower QOL at 12 months follow up compared to non-depressed patients. Targeting depressed patients for intervention may foster a faster recovery and reduce excessive healthcare burden.

Determinants and Outcomes of Vasoplegia Following Left Ventricular Assist Device Implantation.

BACKGROUND: Vasoplegia is associated with adverse outcomes following cardiac surgery; however, its impact following left ventricular assist device implantation is largely unexplored. METHODS AND RESULTS: In 252 consecutive patients receiving a left ventricular assist device, vasoplegia was defined as the occurrence of normal cardiac function and index but with the need for intravenous vasopressors within 48 hours following surgery for >24 hours to maintain a mean arterial pressure >70 mm Hg. We further categorized vasoplegia as none; mild, requiring 1 vasopressor (vasopressin, norepinephrine, or high-dose epinephrine [>5 µg/min]); or moderate to severe, requiring ≥2 vasopressors. Predictors of vasoplegia severity were determined using a cumulative logit (ordinal logistic regression) model, and 1-year mortality was evaluated using competing-risks survival analysis. In total, 67 (26.6%) patients developed mild vasoplegia and 57 (22.6%) developed moderate to severe vasoplegia. The multivariable model for vasoplegia severity utilized preoperative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile, central venous pressure, systolic blood pressure, and intraoperative cardiopulmonary bypass time, which yielded an area under the curve of 0.76. Although no significant differences were noted in stroke or pump thrombosis rates (P=0.87 and P=0.66, respectively), respiratory failure and major bleeding increased with vasoplegia severity (P<0.01). Those with moderate to severe vasoplegia had a significantly higher risk of mortality than those without vasoplegia (adjusted hazard ratio: 2.12; 95% confidence interval, 1.08-4.18; P=0.03). CONCLUSIONS: Vasoplegia is predictive of unfavorable outcomes, including mortality. Risk factors for future research include preoperative INTERMACS profile, central venous pressure, systolic blood pressure, and intraoperative cardiopulmonary bypass time.

Reoperative sternotomy is associated with primary graft dysfunction following heart transplantation.

OBJECTIVES: Prior sternotomy is associated with increased morbidity and mortality following heart transplantation. However, its effect on primary graft dysfunction (PGD), a major contributor to early mortality, is unknown. Herein, this effect is studied using the International Society for Heart and Lung Transplantation consensus definition for PGD. METHODS: Medical records of consecutive adult cardiac transplants between 2012 and 2016 were reviewed. Baseline characteristics, postoperative findings and 1-year survival were compared between patients with and without prior sternotomy. RESULTS: Among 255 total patients included, 139 (55%) had undergone prior sternotomy; these recipients were older, more often male, had higher body mass index, higher frequencies of united network for organ sharing (UNOS) 1A status and ischaemic cardiomyopathy and experienced longer waitlist times when compared with those without prior sternotomy (all P < 0.018). Postoperatively, the prior sternotomy group exhibited higher rates of mild to severe PGD (32% vs 18%; P = 0.015) and higher short-term mortality (P = 0.017) and 1-year mortality (P = 0.047). They required more blood transfusions, had more postoperative pneumonia, wound infection and longer hospital stays. A stepwise multivariable regression model identified prior sternotomy as a predictor of PGD (odds ratio 2.7). Multiple prior sternotomies was associated with even more UNOS 1A status, ischaemic cardiomyopathy and pneumonia. However, logistic modelling did not show a difference in the rate of PGD between those with 1 or ≥2 prior sternotomies. CONCLUSIONS: Our data suggest that prior sternotomy is a risk factor for PGD. Consistent with previous reports, prior sternotomy is associated with increased morbidity, blood product utilization and 1-year mortality following cardiac transplantation.

Repeat Cardiac Transplant Indicated by Severe Cardiac Allograft Vasculopathy in a Patient With Danon Disease.

Danon disease is a rare, X-linked dominant, lysosomal storage disorder, presenting with cardiomyopathy mostly in adolescent men. Male patients face a high mortality rate and rarely live to the age of 25 years unless they receive a heart transplant. Because they generally undergo heart transplantation at a young age, many patients ultimately face both short- and long-term complications. We present a 32-year-old man diagnosed with Danon disease; a nonsense mutation in the LAMP-2 gene. Progressive heart failure symptoms resulted in initial heart transplant at age 27 years. He subsequently developed severe cardiac allograft vasculopathy that led to graft failure requiring a redo orthotopic heart transplant. This is one of only two reported Danon disease cases described to date surviving repeat orthotopic heart transplants. We present this case to highlight the importance of heart transplantation in the management of Danon disease, to emphasize the risk of cardiac allograft vasculopathy post-transplant, and to discuss management strategies.

Prospective Assessment of Frailty Using the Fried Criteria in Patients Undergoing Left Ventricular Assist Device Therapy.

Frail patients are more prone to adverse events after cardiac surgery, particularly after implantation of left ventricular assist devices. Thus, frailty assessment may help identify patients unlikely to benefit from left ventricular assist device therapy. The purpose was to establish a suitable measure of frailty in adults with end-stage heart failure. In a prospective cohort of 75 patients (age 58 ± 12 years) with end-stage heart failure, we assessed the association between frailty (5-component Fried criteria) and the composite primary outcome of inpatient mortality or prolonged length of stay, as well as extubation status, time on ventilator, discharge status, and long-term mortality. Fried frailty criteria were met in 44 (59%) patients, but there was no association with the primary outcome (p = 0.10). However, an abridged set of 3 criteria (exhaustion, inactivity, and grip strength) was predictive of the primary outcome (odds ratio 2.9, 95% confidence interval 1.1 to 7.4), and of time to extubation and time to discharge. In patients with advanced heart failure, the 5-component Fried criteria may not be optimally sensitive to clinical differences. In conclusion, an abridged set of 3 frailty criteria was predictive of the primary outcome and several secondary outcomes, and may therefore be a clinically useful tool in this population.

Abnormally Small Neuromuscular Junctions in the Extraocular Muscles From Subjects With Idiopathic Nystagmus and Nystagmus Associated With Albinism.

PURPOSE: Infantile nystagmus syndrome (INS) is often associated with abnormalities of axonal outgrowth and connectivity. To determine if this manifests in extraocular muscle innervation, specimens from children with idiopathic INS or INS and albinism were examined and compared to normal age-matched control extraocular muscles. METHODS: Extraocular muscles removed during normal surgery on children with idiopathic INS or INS and albinism were immunostained for neuromuscular junctions, myofiber type, the immature form of the acetylcholine receptor, and brain-derived neurotrophic factor (BDNF) and compared to age-matched controls. RESULTS: Muscles from both the idiopathic INS and INS and albinism groups had neuromuscular junctions that were 35% to 71% smaller based on myofiber area and myofiber perimeter than found in age-matched controls, and this was seen on both fast and slow myosin heavy chain isoform-expressing myofibers (all P < 0.015). Muscles from subjects with INS and albinism showed a 7-fold increase in neuromuscular junction numbers on fast myofibers expressing the immature gamma subunit of the acetylcholine receptor. The extraocular muscles from both INS subgroups showed a significant increase in the number and size of slow myofibers compared to age-matched controls. Brain-derived neurotrophic factor was expressed in control muscle but was virtually absent in the INS muscles. CONCLUSIONS: These studies suggest that, relative to the final common pathway, INS is not the same between different patient etiologies. It should be possible to modulate these final common pathway abnormalities, via exogenous application of appropriate drugs, with the hope that this type of treatment may reduce the involuntary oscillatory movements in these children.

Uses of the Inferior Oblique Muscle in Strabismus Surgery.

Inferior oblique muscle weakening is typically performed for overaction of the muscle. In this article, we review inferior oblique muscle anatomy, different weakening procedures, and recent surgical techniques that take advantage of the muscle's unique anatomy for the treatment of additional indications such as excyclotorsion and hypertropia in primary gaze.

Nystagmus and related fixation instabilities following extraction of unilateral infantile cataract in the Infant Aphakia Treatment Study (IATS).

PURPOSE: To study eye movements in a large group of children after the removal of unilateral infantile cataract, and to compare fixation instabilities between treatment groups with or without IOL implantation. METHODS: The Infant Aphakia Treatment Study (IATS) is a randomized, multicenter clinical trial comparing IOL to contact lens (CL) treatment with a unilateral infantile cataract in participants who underwent cataract surgery at 1 to 6 months of age. At age 4.5 years, eye movements were recorded in 103 participants, using a high-speed video camera while the child performed a fixation task. The recordings were inspected by masked readers for the presence of fixation instabilities (nystagmus and saccadic oscillations). RESULTS: Overall, fixation instabilities were observed in 50 (60%) of 83 children who had evaluable recordings, with no differences between treatment groups (27 [64%] of 42 in the IOL group, 23 [56%] of 41 in the CL group; P = 0.51). Nystagmus was seen in 38% and saccadic oscillations in 31%, with no differences between treatment groups (P > 0.33). Children without a fixation instability had better visual acuity (P = 0.04). CONCLUSIONS: Nystagmus and saccadic oscillations are well-known consequences of infantile cataracts, presumably the result of visual deprivation during the critical period of visual development. After early cataract extraction, successful optical correction may reduce further form deprivation and minimize the incidence of these fixation instabilities. In this study, no differences in the presence of fixation instabilities were found between the two treatment strategies (CL or IOL) for optical correction after cataract removal. (ClinicalTrials.gov number, NCT00212134.).

Unilateral lateral rectus resection for horizontal diplopia in adults with divergence insufficiency.

BACKGROUND: Divergence insufficiency (DI) is an acquired comitant strabismus in aging individuals, characterized by esotropia and diplopia at distance. Treatment options include occlusion, base-out prism glasses, and a variety of surgical procedures to the horizontal rectus extraocular muscles. Here, we present a large cohort of patients with DI who underwent unilateral resection of the lateral rectus muscle. This is a simple procedure, typically performed under regional anesthesia and on the non-dominant eye. METHODS: Clinical characteristics and complaints were collected from patients with DI who underwent unilateral lateral rectus resection over a 6.5-year period. Treatment success was evaluated in terms of post-operative symptomatic deviation and the need for prisms in order to achieve sensory fusion. RESULTS: The cohort consisted of 57 patients (age 54-89 years). The majority sought surgical care after prism glasses were no longer tolerated, or after onset of a larger symptomatic deviation (typically 10 to 18 prism diopters). After surgery (minimum 6 weeks follow-up; median 10 weeks), 86.0 % showed successful results with no further treatment; an additional 10.5 % stayed free of diplopia with a post-operative prism (horizontal or vertical), and only two patients (3.5 %) required further surgery and were considered failures. CONCLUSIONS: Mild DI is usually treated with a base-out prism. Treatment of pronounced DI with unilateral lateral rectus resection was generally successful, with 96.5 % not requiring further surgery. Unilateral lateral rectus resection appears to be a valid option for treatment of DI.

Postulating a role for connective tissue elements in inferior oblique muscle overaction (an American Ophthalmological Society thesis).

PURPOSE: To compare the localization and density of collagens I, IV, VI, and elastin, the major protein components of connective tissue, in the inferior oblique muscle of patients with overelevation in adduction and in controls and to characterize changes that develop following surgery. Biomechanical studies suggest that the connective tissue matrix plays a critical role in extraocular muscle function, determining tensile strength and force transmission during contraction. METHODS: Prospective laboratory-based case-control study of inferior oblique muscle specimens from 31 subjects: 16 with primary inferior oblique overaction, 6 with craniofacial dysostosis, and 9 normal controls. Collagen I, IV, VI, and elastin were localized and quantified using immunohistochemical staining. Densities were compared using analysis of variance and post hoc comparisons. RESULTS: In primary inferior oblique overaction, all connective tissue components in unoperated specimens were elevated compared to controls (P<.0001). Previously operated muscles showed normal levels of collagens IV and VI (P>.27) but increased collagen I. In unoperated craniofacial dysostosis specimens, only elastin was elevated (P=.03), whereas density of collagens IV and VI was lower in previously operated vs unoperated specimens (P=.015). CONCLUSIONS: Elevated collagen and elastin levels in the cohort with primary inferior oblique overaction are consistent with the clinical finding of muscle stiffness. Contrarily, normal connective tissue densities in craniofacial dysostosis support the hypothesis that overelevation in this group reflects anomalous muscle vectors rather than tissue changes. Surgical intervention was associated with changes in the connective tissue matrix in both cohorts. These results have ramifications for treating patients with overelevation in adduction.

Eye muscle surgery for infantile nystagmus syndrome in the first two years of life.

PURPOSE: To report visual and elctrophysioloigcal effects of eye muscle surgery in young patients with infantile nystagmus syndrome (INS). METHODS: Prospective, interventional case cohort of 19 patients aged under 24 months who were operated on for combinations of strabismus, an anomalous head posture, and nystagmus. All patients were followed at least nine months. Outcome measures, part of an institutionally approved study, included Teller acuity, head position, strabismic deviation, and eye movement recordings, from which waveform types and a nystagmus optimal foveation fraction (NOFF). Computerized parametric and nonparametric statistical analysis of data were perfomed using standard software on both individual and group data. RESULTS: Age averaged 17.7 months (13.1-month follow-up). Thirteen (68%) patients had associated optic nerve or retinal disease. 42% had amblyopia, 68% had refractive errors. Group means in binocular Teller acuity (P < 0.05), strabismic deviation (P < 0.05), head posture (P < 0.001), and the NOFF measures (P < 0.01) from eye movement recordings improved in all patients. There was a change in null zone waveforms to more favorable jerk types. There were no reoperations or surgical complications. CONCLUSIONS: Surgery on the extraocular muscles in patients aged less than two years with INS results in improvements in multiple aspects of ocular motor and visual function.