Inhibition of MET Signaling with Ficlatuzumab in Combination with Chemotherapy in Refractory AML: Clinical Outcomes and High-Dimensional Analysis.

Acute myeloid leukemia patients refractory to induction therapy or relapsed within one year have poor outcomes. Autocrine production of hepatocyte growth factor by myeloid blasts drives leukemogenesis in pre-clinical models. A phase Ib trial evaluated ficlatuzumab, a first-in-class anti-HGF antibody, in combination with cytarabine in this high-risk population. Dose-limiting toxicities were not observed, and 20 mg/kg was established as the recommended phase II dose. The most frequent treatment-related adverse event was febrile neutropenia. Among 17 evaluable patients, the overall response rate was 53%, all complete remissions. Phospho-proteomic mass cytometry showed potent on-target suppression of p-MET after ficlatuzumab treatment and that attenuation of p-S6 was associated with clinical response. Multiplexed single cell RNA sequencing using prospectively acquired patient specimens identified interferon response genes as adverse predictive factors. The ficlatuzumab and cytarabine combination is well-tolerated with favorable efficacy. High-dimensional analyses at single-cell resolution represent promising approaches for identifying biomarkers of response and mechanisms of resistance in prospective clinical studies.

Retrobulbar anaesthesia for adjustable strabismus surgery in adults: a prospective observational study.

OBJECTIVE: To characterize the ocular response to retrobulbar anaesthesia and to evaluate the efficacy of retrobulbar anaesthesia for adjustable strabismus surgery in adults. DESIGN: Prospective observational study. PARTICIPANTS: Adult patients undergoing adjustable strabismus surgery under retrobulbar anaesthesia. METHODS: Surgical success was defined by ocular alignment within 10 prism diopters (PD) of orthotropia for horizontal rectus surgery and within 5 PD for vertical rectus surgery. After retrobulbar injection of Xylocaine with epinephrine, the onset time and the degree of visual impairment, ocular akinesia, and analgesia were evaluated. Postoperative parameters included the restoration of vision, onset of pain, resolution of ptosis, normalization of pupil, resolution of extraocular motility deficits, and the timing of postoperative adjustment. Perioperative complications were also documented. RESULTS: A total of 33 patients were initially included in this study. Two patients experienced complications (perioperative retrobulbar hemorrhage, postoperative suprachoroidal hemorrhage) and were excluded from data analysis. Of the remaining 31 patients (mean age, 50.2 ± 14.8 years), surgical outcome was satisfactory in 30/31 (96.8%) patients at the first postoperative visit and in 15/19 (78.9%) cases at last follow-up (mean, 6.1 ± 1.6 months). Excellent intraoperative ocular akinesia and analgesia was achieved with retrobulbar anaesthesia. After retrobulbar injection, visual impairment was the first to resolve to preoperative levels within (mean ± SD) 3.7 ± 1.9 hours postinjection, followed by onset of pain at 4.1 ± 1.0 hours, resolution of ptosis at 4.3 ± 1.9 hours, and normalization of pupil reactivity at 6.1 ± 1.0 hours. The resolution of anaesthesia upon extraocular motility occurred within 5.7 ± 1.0 hours postinjection (range, 4.5-8.0 hours), allowing for subsequent same-day postoperative adjustment. CONCLUSIONS: Retrobulbar anaesthesia in the context of adult, adjustable strabismus surgery is a relatively safe and effective technique. It provides excellent intraoperative analgesia and akinesia. Retrobulbar anaesthesia enables for same-day suture adjustments to be reliably performed.

Clinical profiles and surgical outcomes of adult esotropia.

OBJECTIVE: The aim of this study was to describe the clinical features and surgical outcomes of teenage and adult patients with esotropia undergoing strabismus surgery with adjustable sutures. METHODS: Seventy-three patients were included in this retrospective, cohort study. Patients were stratified into group 1 (35 with childhood-onset esotropia [CET]) and group 2 (38 with adult-onset esophoria-tropia [EPT]). Preoperative immediate, 2-week, and 4-6-month postoperative measurements of ocular alignment, as well as fusional testing, were performed. Postoperative success was defined as distant (6 m) and near (33 cm) alignment within 12 prism diopters (PDs) of orthotropia in the primary position at 2 weeks and at 4-6 months with a single surgery. RESULTS: Patients with CET more frequently had hyperopia and amblyopia and were more likely to present for surgery because of psychosocial strabismus-related problems. Patients with EPT predominantly had myopia and were more likely to experience diplopia and asthenopia. In group 1, the mean preoperative distance deviation improved from 30 PDs to 4 PDs at 2 weeks and to 4 PDs at 4-6 months (p < 0.001). In group 2, mean preoperative distance alignment improved from 22 to 3 PDs at 2 weeks and to 3 PDs at 4-6 months (p < 0.001). The mean objective, single-surgery success rate at 2 weeks was 88% and 97% in groups 1 and 2, respectively. At 4-6 months, postoperative success was 71% in group 1 and 80% in group 2. The majority of patients reported subjective improvement. CONCLUSIONS: There are distinct preoperative differences between CET and EPT patients. Adjustable, strabismus surgery in this cohort is safe and effective in achieving subjective and objective success.

Surgical Management of Unilateral Superior Oblique Palsy: Thirty Years of Experience.

INTRODUCTION AND PURPOSE: We describe the clinical characteristics of 252 patients with unilateral superior oblique palsy who underwent strabismus surgery. We assess if a predetermined surgical strategy, based on preoperative alignment and motility measurements, was effective in treating these patients. On this basis, the patients were divided into three different treatment groups. METHODS: Two-hundred fifty-two patients were identified retrospectively and classified into three groups according to the performed procedures: 1) inferior oblique weakening; 2) inferior rectus recession; 3) combined inferior oblique weakening and inferior rectus recession. Demographic and clinical data were recorded. Criteria for surgical success included good postoperative alignment (distance, primary position alignment ≤5Δ), and improvement of diplopia and of abnormal head posture. Subgroup analyses of surgical outcome were performed for small (<12Δ) versus large (>20Δ) preoperative hypertropia in the group that underwent inferior oblique weakening, and for inferior oblique disinsertion-myectomy versus inferior oblique recession. RESULTS: Mean forced primary position (PP) hypertropia decreased from 14.3Δ (range 3-37Δ) to 4.5Δ (range 0-30Δ) in Group 1, from 13Δ (range 1-30Δ) to 2Δ (range -20-20Δ) in Group 2, and from 25.7Δ (range 6-40Δ) to 1.3Δ (range -12-18Δ) in Group 3. Group 1 had the lowest re-operation rate (7.6%), followed by Group 2 (16%) and Group 3 (25.9%). Final surgical success rates were similar in three groups. Inferior oblique weakening was more predictable for small primary position hypertropia, but still yielded 85% success rate in large deviations. Inferior oblique disinsertion-myectomy resulted in more favorable results than inferior oblique recession (P < 0.05). CONCLUSION: When a predetermined surgical strategy is applied to individual patients with unilateral superior oblique palsy, excellent functional improvement can be achieved in the majority of patients.

Adjustable surgical treatment of adult exotropia: postoperative target angles and surgical success.

OBJECTIVES: This study had 3 objectives: (i) to characterize clinical profiles of adults with consecutive exotropia (CXT), intermittent exotropia (IXT), and sensory exotropia (SXT); (ii) to correlate immediate postoperative target angles with successful long-term ocular alignment; and (iii) to compare the efficacy of adjustable versus nonadjustable medial rectus resection ± advancement. STUDY DESIGN: Retrospective, observational, and interventional cohort study. PARTICIPANTS: A total of 133 adult exotropic patients treated surgically at 3 different hospitals between July 2012 and June 2013. METHODS: The patients were divided according to clinical profiles (CXT, IXT, and SXT) based on ophthalmic and orthoptic assessments. Two treatment groups were established: group I-adjustable medial rectus resection ± advancement and adjustable lateral rectus recession; group II-nonadjustable medial resection ± advancement and adjustable lateral rectus recession. Measurements of immediate postadjustment alignment (target angle) and 4-6 months of follow-up alignment were performed and compared between groups. Surgical success was defined as distance primary position alignment within 10 prism diopters (PD) of orthotropia 4-6 months postoperatively. RESULTS: Comparison of clinical profile groups showed that CXT patients had more hyperopia and amblyopia and smaller preoperative deviations; IXT patients had more diplopia and larger preoperative deviations (near > distance); and SXT patients had poor vision in the deviating eye and larger preoperative deviations. Immediate postoperative alignment was 5.2 PD of esodeviation in group I and 3.2 PD of esodeviation in group II. Overall success rates for ocular alignment at 4-6 months postoperatively were comparable with both surgical techniques (74.6% for group I and 74.3% for group II). Patients with a preoperative deviation ≥40 PD had a lower surgical success rate (63.8%) than patients with a deviation <40 PD (80%). Patients presenting with a significant (-1 or worse) abduction deficit in the operated eye at their first visit after surgery had a better success rate at 4-6 months' follow-up (83.3% vs 67.8%). CONCLUSIONS: Adjustable and nonadjustable medial rectus surgeries seem equally successful. Creation of an abduction deficit in the early postoperative period seems predictive of a better outcome. Larger preoperative angles (≥40 PD) were associated with more exotropic drift and a lower percentage of surgical success. Future studies will continue to search for surgical strategies and the ideal target angle that will produce the best long-term alignment stability.

Long-term outcomes of patients with intermediate-risk acute myeloid leukemia treated with autologous hematopoietic cell transplant in first complete remission.

In 2014, autologous hematopoietic cell transplant (autoHCT) was removed from the National Comprehensive Cancer Network guidelines as a recommended treatment for patients with intermediate-risk AML in first complete remission (CR1). We reviewed the outcomes of all patients with intermediate-risk AML treated with autoHCT in CR1 at our institution. Of 334 patients who underwent autoHCT for AML between 1988 and 2013, 133 patients with intermediate-risk AML in CR1 were identified. Cytogenetics were diploid in 97 (73%). With a median follow-up of 4.1 years (range 0.1-17), median overall survival (OS) is 6.7 years; at 5 years post-transplant, 59% of patients remain alive and 43% remain relapse-free. Forty-eight percent of relapsing patients proceeded to salvage alloHCT. Our findings demonstrate that nearly half of patients with intermediate-risk AML in CR1 achieve sustained remissions, and that salvage alloHCT is feasible in those who relapse. AutoHCT therefore remains a reasonable option for intermediate-risk patients with AML in CR1.

Duane syndrome: Clinical features and surgical management.

OBJECTIVE: To further define the clinical features of Duane syndrome and analyze the surgical outcomes in a subset of these patients. DESIGN: Retrospective chart review. PARTICIPANTS: A retrospective chart review of 75 patients with Duane syndrome was performed. METHODS: Complete ophthalmologic and orthoptic data were extracted from the patients' charts, and patients were classified into group I, II, or III based on forced primary position (PP) deviation. Eighteen patients had strabismus surgery to correct the ocular misalignment with its related abnormal head posture. RESULTS: Fifty-six percent of the cases were in group I, 16% in group II, and 28% in group III. Fifty-seven percent were female, 91% were unilateral, and 66% had left eye involvement. Ninety-six percent had fissure-narrowing/globe retraction on adduction; 67% had an upshoot, downshoot, or both; and 63% had an A, V, or X pattern. The A patterns correlated with downshoots in 100% of cases, V patterns with upshoots in 88%, and X patterns with upshoots/downshoots in 100%. In the 18 surgical candidates, there were 14 patients in group I, 4 in group II, and 0 in group III. An excellent surgical outcome occurred in 78% of patients and a fair-to-poor outcome in 22%. Upshoots/downshoots and fissure-narrowing/globe retraction patients showed modest improvement after surgery. CONCLUSIONS: There was a consistent relationship among the type of strabismus, head position, and motility defect. The type of upshoot/downshoot correlated strongly with the A, V, or X pattern. Postoperative improvements of abnormal head posture and PP alignment were achieved in the surgical subset of patients.

Restrictive strabismus: diagnosis and management.

INTRODUCTION: Restrictive strabismus is a type of ocular misalignment with limitation of motility caused by intrinsic or extrinsic mechanical forces. The clinical spectrum of either purely or partially restrictive strabismus is very broad. Most cases are of congenital, traumatic, endocrine, post-paralytic or myopathic origin. The surgical treatment strategies are designed to correct abnormal head posture, to eliminate diplopia in primary and functional positions of gaze and to enhance aesthetic and psychosocial aspects of a patient's life. PURPOSE: The objective of this paper is to present a clinical approach to the diagnosis and evaluation of patients with restrictive strabismus and to propose a logical surgical approach to the correction of this type of ocular misalignment. PATIENTS AND METHODS: As representative of the broad spectrum of restrictive strabismus problems, twelve cases are presented and the preoperative and postoperative clinical finding are illustrated with photographs. CONCLUSION: The clinical spectrum of either purely or partially restrictive strabismus is very broad. The clinical evaluation of patients with this problem must include a careful and detailed history, which is crucial to establishing the diagnosis and must also explore the patient's concerns. Analysis of fixation, head posture, and ocular alignment require both traditional and special examination techniques. Patient and surgeon expectations must be synchronized preoperatively. A variety of surgical strategies can be applied to improve head posture, eliminate diplopia, and improve cosmesis.

Association of HLA-DRB1-restricted CD4⁺ T cell responses with HIV immune control.

The contribution of HLA class II-restricted CD4(+) T cell responses to HIV immune control is poorly defined. Here, we delineated previously uncharacterized peptide-DRB1 restrictions in functional assays and analyzed the host genetic effects of HLA-DRB1 alleles on HIV viremia in a large cohort of HIV controllers and progressors. We found distinct stratifications in the effect of HLA-DRB1 alleles on HIV viremia, with HLA-DRB1*15:02 significantly associated with low viremia and HLA-DRB1*03:01 significantly associated with high viremia. Notably, a subgroup of HLA-DRB1 variants linked with low viremia showed the ability to promiscuously present a larger breadth of peptides with lower functional avidity when compared to HLA-DRB1 variants linked with high viremia. Our data provide systematic evidence that HLA-DRB1 variant expression has a considerable impact on the control of HIV replication, an effect that seems to be mediated primarily by the protein specificity of CD4(+) T cell responses to HIV Gag and Nef.

Expansion of HIV-specific T follicular helper cells in chronic HIV infection.

HIV targets CD4 T cells, which are required for the induction of high-affinity antibody responses and the formation of long-lived B cell memory. The depletion of antigen-specific CD4 T cells during HIV infection is therefore believed to impede the development of protective B cell immunity. Although several different HIV-related B cell dysfunctions have been described, the role of CD4 T follicular helper (TFH) cells in HIV infection remains unknown. Here, we assessed HIV-specific TFH responses in the lymph nodes of treatment-naive and antiretroviral-treated HIV-infected individuals. Strikingly, both the bulk TFH and HIV-specific TFH cell populations were significantly expanded in chronic HIV infection and were highly associated with viremia. In particular, GAG-specific TFH cells were detected at significantly higher levels in the lymph nodes compared with those of GP120-specific TFH cells and showed preferential secretion of the helper cytokine IL-21. In addition, TFH cell expansion was associated with an increase of germinal center B cells and plasma cells as well as IgG1 hypersecretion. Thus, our study suggests that high levels of HIV viremia drive the expansion of TFH cells, which in turn leads to perturbations of B cell differentiation, resulting in dysregulated antibody production.

Partial third cranial nerve palsy: clinical characteristics and surgical management.

PURPOSE: Incomplete recovery from injury to the third cranial nerve results in ocular misalignment and associated diplopia. Our aim in this study was to describe and evaluate strabismus surgery strategies aimed at restoring functional, single binocular vision in this population. DESIGN: Retrospective review. PARTICIPANTS: We studied 12 adult patients with acquired partial third cranial nerve palsy who underwent strabismus surgery. METHODS: The 12 consecutive patients with residual third nerve palsy were selected from among the patients seen between 2000 and 2010 in the clinical practice of 1 strabismologist (M.F.). Complete pre- and postoperative ophthalmologic and orthoptic examinations were performed in each patient. The patients presented with isolated hypotropias (n = 7) and exohypotropias (n = 5). Strabismus surgery included: contralateral superior rectus recession, ipsilateral inferior rectus recession, vertical transposition of horizontal recti, horizontal rectus muscle surgery, or combined horizontal and vertical muscle surgery. Complete surgical success was defined as postoperative alignment within 5 prism diopters (PD) of orthotropia and the absence of diplopia in functional positions of gaze. The average follow-up was 23 months (range, 7 to 81 months). RESULTS: The mean preoperative vertical and horizontal deviations were 19 PD hypotropia (8-40 PD) and 19 PD exotropia (6-40 PD), respectively. The mean postoperative deviations were 2 PD hypotropia (0-8 PD) and 1 PD exotropia (0-6 PD). Complete surgical success was achieved in 7 of 12 patients. Partial success was attained in 5 of 12 patients, who experienced significant improvement but required postoperative use of a prism. CONCLUSIONS: This study indicates that patients with incomplete third cranial nerve paralysis may enjoy good functional and cosmetic outcomes with strabismus surgery.

HIV-specific cytolytic CD4 T cell responses during acute HIV infection predict disease outcome.

Early immunological events during acute HIV infection are thought to fundamentally influence long-term disease outcome. Whereas the contribution of HIV-specific CD8 T cell responses to early viral control is well established, the role of HIV-specific CD4 T cell responses in the control of viral replication after acute infection is unknown. A growing body of evidence suggests that CD4 T cells-besides their helper function-have the capacity to directly recognize and kill virally infected cells. In a longitudinal study of a cohort of individuals acutely infected with HIV, we observed that subjects able to spontaneously control HIV replication in the absence of antiretroviral therapy showed a significant expansion of HIV-specific CD4 T cell responses-but not CD8 T cell responses-compared to subjects who progressed to a high viral set point (P = 0.038). Markedly, this expansion occurred before differences in viral load or CD4 T cell count and was characterized by robust cytolytic activity and expression of a distinct profile of perforin and granzymes at the earliest time point. Kaplan-Meier analysis revealed that the emergence of granzyme A(+) HIV-specific CD4 T cell responses at baseline was highly predictive of slower disease progression and clinical outcome (average days to CD4 T cell count <350/µl was 575 versus 306, P = 0.001). These data demonstrate that HIV-specific CD4 T cell responses can be used during the earliest phase of HIV infection as an immunological predictor of subsequent viral set point and disease outcome. Moreover, these data suggest that expansion of granzyme A(+) HIV-specific cytolytic CD4 T cell responses early during acute HIV infection contributes substantially to the control of viral replication.

HIV-specific CD4 T cell responses to different viral proteins have discordant associations with viral load and clinical outcome.

A successful prophylactic vaccine is characterized by long-lived immunity, which is critically dependent on CD4 T cell-mediated helper signals. Indeed, most licensed vaccines induce antigen-specific CD4 T cell responses, in addition to high-affinity antibodies. However, despite the important role of CD4 T cells in vaccine design and natural infection, few studies have characterized HIV-specific CD4 T cells due to their preferential susceptibility to HIV infection. To establish at the population level the impact of HIV-specific CD4 T cells on viral control and define the specificity of HIV-specific CD4 T cell peptide targeting, we conducted a comprehensive analysis of these responses to the entire HIV proteome in 93 subjects at different stages of HIV infection. We show that HIV-specific CD4 T cell responses were detectable in 92% of individuals and that the breadth of these responses showed a significant inverse correlation with the viral load (P = 0.009, R = -0.31). In particular, CD4 T cell responses targeting Gag were robustly associated with lower levels of viremia (P = 0.0002, R = -0.45). Importantly, differences in the immunodominance profile of HIV-specific CD4 T cell responses distinguished HIV controllers from progressors. Furthermore, Gag/Env ratios were a potent marker of viral control, with a high frequency and magnitude of Gag responses and low proportion of Env responses associated with effective immune control. At the epitope level, targeting of three distinct Gag peptides was linked to spontaneous HIV control (P = 0.60 to 0.85). Inclusion of these immunogenic proteins and peptides in future HIV vaccines may act as a critical cornerstone for enhancing protective T cell responses.

Epithelial adhesion molecules can inhibit HIV-1-specific CD8⁺ T-cell functions.

Under persistent antigenic stimulation, virus-specific CD8⁺ T cells become increasingly dysfunctional and up-regulate several inhibitory molecules such as killer lectin-like receptor G1 (KLRG1). Here, we demonstrate that HIV-1 antigen-specific T cells from subjects with chronic-progressive HIV-1 infection have significantly elevated KLRG1 expression (P < .001); show abnormal distribution of E-cadherin, the natural ligand of KLRG1, in the intestinal mucosa; and have elevated levels of systemic soluble E-cadherin (sE-cadherin) that significantly correlate with HIV-1 viral load (R = 0.7, P = .004). We furthermore demonstrate that in the presence of sE-cadherin, KLRG1(hi) HIV-1-specific CD8⁺ T cells are impaired in their ability to respond by cytokine secretion on antigenic stimulation (P = .002) and to inhibit viral replication (P = .03) in vitro. Thus, these data suggest a critical mechanism by which the disruption of the intestinal epithelium associated with HIV-1 leads to increased systemic levels of sE-cadherin, which inhibits the effector functions of KLRG1(hi)-expressing HIV-1-specific CD8⁺ T cells systemically.

HIV-1-specific interleukin-21+ CD4+ T cell responses contribute to durable viral control through the modulation of HIV-specific CD8+ T cell function.

Functional defects in cytotoxic CD8(+) T cell responses arise in chronic human viral infections, but the mechanisms involved are not well understood. In mice, CD4 cell-mediated interleukin-21 (IL-21) production is necessary for the maintenance of CD8(+) T cell function and control of persistent viral infections. To investigate the potential role of IL-21 in a chronic human viral infection, we studied the rare subset of HIV-1 controllers, who are able to spontaneously control HIV-1 replication without treatment. HIV-specific triggering of IL-21 by CD4(+) T cells was significantly enriched in these persons (P = 0.0007), while isolated loss of IL-21-secreting CD4(+) T cells was characteristic for subjects with persistent viremia and progressive disease. IL-21 responses were mediated by recognition of discrete epitopes largely in the Gag protein, and expansion of IL-21(+) CD4(+) T cells in acute infection resulted in lower viral set points (P = 0.002). Moreover, IL-21 production by CD4(+) T cells of HIV controllers enhanced perforin production by HIV-1-specific CD8(+) T cells from chronic progressors even in late stages of disease, and HIV-1-specific effector CD8(+) T cells showed an enhanced ability to efficiently inhibit viral replication in vitro after IL-21 binding. These data suggest that HIV-1-specific IL-21(+) CD4(+) T cell responses might contribute to the control of viral replication in humans and are likely to be of great importance for vaccine design.

Optimal compliance for amblyopia therapy: occlusion with a translucent tape on the lens.

OBJECTIVE: To demonstrate that optimal compliance to amblyopia therapy and a better visual outcome can be achieved by occluding the lens over the preferred eye with a translucent tape. STUDY DESIGN: Prospective study of amblyopic children. PARTICIPANTS: Eighty-four amblyopic children recruited from 2000 to 2006 at the Montreal Children's Vision Centre. METHODS: A group of bilateral ametropes (mean age 3.8 years) were treated with glasses and occlusion of the sound eye with a translucent tape on the lens over the preferred eye, or an adhesive patch. The translucent tape reduced vision to hand motion at 0.3 m in the sound eye. Patients were divided into 2 groups depending on the treatment received. Group 1 (n = 36) was occluded with a translucent tape, and group 2 (n = 48) with a conventional adhesive patch, later replaced by the translucent tape. Twenty-five previously reported patients, treated with the conventional adhesive patch only, were used as controls (group 3). RESULTS: The mean amblyopic visual acuity was 20/100-2. Compliance was good in 36 patients (group 1), and was poor or deteriorated in 24/48 patients (group 2). Substituting the adhesive patch with a translucent tape permitted uninterrupted and prolonged occlusion, with a successful visual outcome. The amblyopic eye achieved a significantly better final vision (20/30+2; groups 1+2) than the controls (20/40+1; group 3) (p = 0.04). Sixty-four (76.19%) patients achieved >or=20/30. CONCLUSIONS: The translucent tape optimizes compliance and yields better vision by lengthening the duration of occlusion therapy and reducing the number of treatment failures due to noncompliance.

Acquired restrictive strabismus and high axial myopia: diagnosis and management.

OBJECTIVE: This paper documents the clinical, ultrasound, magnetic resonance imaging (MRI), and anatomic characteristics of 6 patients with esohypotropia and high axial myopia. The results of strabismus surgery performed on these patients are evaluated. STUDY DESIGN: Retrospective cohort study. PARTICIPANTS: Six patients with esohypotropia and high axial myopia were selected from the practice of the second author (Michael Flanders). METHODS: We extracted the history and data from the preoperative and postoperative ophthalmic and orthoptic examinations, recorded the surgical procedures, and tabulated the postoperative results. A- and B-scans, orbital MRI images, and photo documentation were obtained for all patients. Supramaximal recession and resection on the horizontal rectus muscles, using adjustable sutures, was performed in all patients. A surgical outcome was deemed successful if, in primary position, postoperative horizontal ocular alignment measured 15 prism diopters (PD) or less and (or) if diplopia was eliminated. RESULTS: Echographic and MRI findings demonstrated an enlarged globe in all cases. Globe flattening on the orbital walls was found in 5 cases. Lateral rectus depression was visualized on MRI images in 4 cases. Surgical success was obtained in all patients. The average preoperative primary position esotropia measured 60 PD (25 to 90 PD) and the esodeviation after surgery was 7.0 PD (0 to 15 PD). Ductions were also improved. CONCLUSIONS: Different surgical approaches to realignment of eyes with high myopia and esohypotropia have been attempted. In this study, supramaximal amounts of recession and resection on the rectus muscles provided satisfactory results.