Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial.

A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).

Varying development of femoral and tibial subchondral bone tissue and their interaction with articular cartilage during progressing osteoarthritis.

INTRODUCTION: Differences between tibial and femoral joint surfaces and knee compartments concerning coupled bone and cartilage turnover or bone-cartilage cross talk have not been previously examined, although the mechanical and biological interaction of the mineralized subchondral tissues with articular cartilage is of great importance for advancing osteoarthritis. MATERIALS AND METHODS: Therefore, with the help of immunohistochemistry and real-time polymerase chain reaction (RT-PCR), human knee joint cartilage tissue was investigated for expression of key molecules of the extracellular matrix and cartilage composition (collagen type I and II, aggrecan) plus proteoglycan content (colorimetric analysis). Furthermore, we correlated the results with 3D microcomputed tomography of the underlying subchondral bone (high-resolution micro-CT system). Measurements were performed in dependence of the anatomical site (femoral vs. tibial, medial and lateral each) to identify regional differences during the osteoarthritic process. From an enduring series of 108 patients undergoing implantation of TKA, 34 osteochondral samples with lesions macroscopically classified as ICRS grade 1b (group A) and 34 samples with ICRS grade 3a/3b lesions (group B) were compared with 21 healthy controls. RESULTS: Concerning 3D analysis, the medial femoral condyle and tibia showed the most significant increase in bone volume fraction and a decrease in the trabecular number in group B frequently accompanied by subchondral bone resorption pits and enchondral ossification. Under physiological conditions, tibia plateaus show lower bone volume fraction than the corresponding femoral site and this difference enlarges with advancing OA. Partially even contradictory behavior was observed such as trabecular separation at the lateral tibial and medial plateau in osteochondral OA samples of the same patients. Collagen type II expression levels show faster and varying changes than type I during the OA process, leading to a lower positive or negative correlation with bone microstructural analysis, especially on the tibia plateau. CONCLUSIONS: Structural bone and cartilage parameter changes showed varying developments and correlations among each other in the different compartments of the knee. As a clinical conclusion, therapies to postpone or prevent cartilage degeneration by influencing the loss of mineralized bone could be site dependent.

Post-transfusion purpura in a woman with acute myeloid leukemia.

Post-transfusion purpura (PTP) is a rare, but severe transfusion reaction in which both donor and autologous platelets are sequestered due to immunization against HPA-1a antigens in HPA-1a negative recipients (HPA: human platelet antigens). We describe a patient who developed PTP during induction therapy for acute myeloid leukaemia. The pitfalls, delays in diagnosing and therapy options of this serious transfusion reaction are discussed.

[Evaluation of the medical treatment situation of the visually impaired : Significant differences between young and old]. / Evaluation der Versorgungssituation von Sehbehinderten : Signifikante Unterschiede zwischen Jung und Alt.

BACKGROUND AND OBJECTIVE: Patients with irreversible visual impairment need individual visual rehabilitation to regain or improve reading ability and mobility. To analyze the prescription of low vision aids (LVA) and their relation to age, we performed a retrospective chart analysis of our specialized low vision outpatient clinic. METHODS: Patient charts of all patients who attended our low vision outpatient clinic from 2014-2016 were analyzed with respect to the diagnosis, visual acuity, magnification needs, age and prescribed or used LVA. RESULTS: The evaluation comprised data from 1548 patients (age 0-97 years). Most patients (72%) were underage (<18 years). Retinoblastoma (11%), congenital cataract (10%) and age-related macular degeneration (AMD, 6%) were the most frequent diagnoses. Mean magnification need of the 568 patients with LVAs was 9.9 ± 7. Desktop video magnifiers (22%), cut-off filter spectacles (15%) and electronic magnifiers (13%) were most commonly prescribed. Children and juveniles used smart phones and tablets (smart devices) as a LVA significantly more often (8% vs. 0.6%, p < 0.01) compared to older visually impaired patients (>60 years). Electronic magnifying devices were more often prescribed to these older patients (30% vs. 3%, p < 0.01). CONCLUSION: The visual rehabilitation showed significant differences between underage and older visually impaired patients. Children and juveniles needed electronic magnifiers less often because they used smart devices as a mobile LVA. This significant difference might be due to much lower social stigmatization of smart devices and the higher affinity to technology of this age group. Based on the positive experiences of younger visually impaired patients, such smart devices should also be introduced to older patients.

The Effect of Early Thyroidectomy on the Course of Active Graves' Orbitopathy (GO): A Retrospective Case Study.

The aim of the work was to investigate the effect of early thyroidectomy on the course of active Graves' orbitopathy (GO) in patients with low probability of remission [high TSH receptor antibody (TRAb) serum levels, severe GO] compared to that of continued therapy with antithyroid drugs. Two cohorts were evaluated retrospectively (total n=92 patients with active GO, CAS≥4). Forty-six patients underwent early thyroidectomy (Tx-group) 6±2 months after initiation of antithyroid drug (ATD) therapy, while ATD was continued for another 6±2 months in the ATD-group (n=46). These controls were consecutively chosen from a database and matched to the Tx-group. GO was evaluated (activity, severity, TRAb) at baseline and at 6 month follow-up. At baseline, both cohorts were virtually identical as to disease severity, activity and duration, as well as prior anti-inflammatory treatment, age, gender, and smoking behavior. At 6 month follow-up, NOSPECS severity score was significantly decreased within each group, but did not differ between both groups. However, significantly more patients of the Tx-group presented with inactive GO (89.1 vs. 67.4%, * p=0.02), and mean CAS score was significantly lower in Tx-group (2.1) than in ADT-group (2.8; * p=0.02) at the end of follow-up. TRAb levels declined in both groups (Tx-group: from 18.6 to 5.2 vs. ATD-group: 12.8-3.2 IU/l, p0=0.07, p6months=0.32). Residual GO activity was lower in Tx-group, associated with a higher rate of inactivation of GO. This allows an earlier initiation of ophthalmosurgical rehabilitation in patients with severe GO, which may positively influence quality of life of the patients.

[Important Aspects of Diagnosis and Minimally Invasive Treatment of Metastases in the Spine Through the Plasma Field Therapy (Cavity Coblation Method)]. / Besonderheiten der Diagnostik und der minimalinvasiven chirurgischen Behandlung von multiplen Metastasen an der Wirbelsäule durch Plasmafeldtherapie (Cavity-Coblation-Methode).

Background and objectives: Until recently, it was almost impossible to perform major surgery on metastases in the spine. This is especially the case for multiple spinal metastases and for older multi-morbid patients with higher OP risks. It is very important in such cases that the operation should be as minimally invasive as possible, and should aim to reduce pain, treat fractures and to improve the quality of life. The aim of this publication is to present and discuss the specific features of the methodology, problems, surgical techniques, as well as the effectiveness of the modernised cavity/coblation method and results of the treatment of 240 patients with spine metastases. Patients/Material and Method: Patients: Patients of every age with bone destruction were treated, with osteolysis and pathological fractures of vertebrae caused by metastases. The pre-operative diagnosis was evaluated by X-Ray, MRT, CT, whole-body F18-FDG-PET, whole-body bone scintigraphy, histology. Cavity/coblation method: Tumour resection was carried out by the plasma field (42 °C, cold energy) over the percutaneous trans-/extrapedicular access and was followed by balloon kyphoplasty. Tumour tissue was removed, deformation corrected and stability enhanced. The treatment clearly reduced the risks of recurrence, fracture and compression of the neural structures. Local radiotherapy and chemotherapy were performed post-operatively. Clinical and radiological follow-ups, included tumour staging, were performed regularly after the OP (after 2 and 14 days and 3, 6,12, 24, 36, 48 and 60 months), including data on pain and improvement in quality of life. Results: Within 6 years (03/08-04/14), we treated 240 patients with multiple spinal metastases (146 female, 94 male, age range 31-92 years, average age 65.5 years) or 784 vertebral bodies. 61 patients were also given dorsal percutaneous instrumentation and straightening. All patients experienced a significant reduction in pain, and improvements in satisfaction and quality of life. Treatment was combined with chemotherapy and local radiotherapy to reduce tumour cell growth or recurrence rate. Patients could be rapidly mobilised after surgery, blood loss was minimal, and the next oncology treatment could be initiated immediately. Discussion/Conclusions: Cavity/coblation is a safe and minimally invasive procedure, as confirmed by our own short- and long-term results, as well as by reports/publications of other workers. OP risks, blood loss, and surgical time are lower and shorter. This new method is very promising for the future. It is important that the indication is correct and the treatment strategy must be adapted individually. Prognosis must be assessed and the surgical technique must be precise.

[Graves' ophthalmopathy]. / Endokrine Orbitopathie.

Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease and the full clinical picture can impair the quality of life of the patients considerably. Active inflammation can often be effectively treated by intravenous steroids/immunosuppression, however does not lead to full remission, since inflammation rather quickly results in irreversible fibrosis and increase of orbital fat. Very important is the control of risk factors (smoking cessation, good control of thyroid function, selenium supplementation) to prevent progression to severe stages. Treatment should rely on a thorough assessment of activity and severity of GO. Rehabilitative surgery (orbital decompression, squint surgery, eyelid surgery) is needed in many patients to restore function and appearance. Anti-thyroid-stimulating hormone (TSH) receptor antibodies do specifically occur in these patients and correlate to the course of thyroid and eye disease. The levels of these antibodies can be used for treatment decisions at certain time points of the disease.

[Contralateral Recession of the Inferior Oblique Muscle in Grave's Disease Patients with Mild M. rectus inferior fibrosis]. / Prinzip Gegenparese: M.-obliquus-inferior-Rücklagerung bei Patienten mit endokriner Orbitopathie.

INTRODUCTION: The aim of this study was to evaluate the dose effect and the resulting binocular single vision for inferior oblique muscle recession in patients with Grave's orbitopathy. METHODS AND PATIENTS: The evaluation covered all patients (n = 13) between 2010-2013 treated with recession of the inferior oblique muscle for vertical deviation caused by inferior fibrosis of the contralateral eye. The inclusion criterion was a small vertical squint angle with excyclotorsion. The corrected vertical squint angle was 3.75° [7 pdpt] (median, min 1.5° [3 pdpt], max 8° [16 pdpt]) in primary position and 5.5° in adduction [11pdpt] (median, min 3°[6 pdpt], max 9°[18pdpt]). Excyclotorsion was 4° [8 pdpt] (median, min 1° [2 pdpt], max 9° [18 pdpt]). Elevation was only slightly impaired and the side difference was 5° (median). The recession distance was preoperatively determined: 0.5° squint angle reduction per mm recession distance (calculation from patients who received surgery before 2010). RESULTS: Inferior oblique recession generated a good field of binocular single vision (BSV) for all patients. All patients reached BSV in the central area (20°) and within 30° of downgaze. Sixty nine percent of the patients were completely diplopia free in downgaze. Diplopia persisted in more than half of the patients in up gaze outside 15°. Squint reduction was 0.5° [1 pdpt] [0.45-0.67]/per mm recession distance in primary position and 0.65° [1.3 pdpt] [0.55-0.76]/per mm for the vertical deviation in adduction. Excyclotorsion was reduced to ≤ 2° in 77 % of the patients. CONCLUSION: Inferior oblique muscle recession can be very successfully performed on the contralateral eye in patients with mild inferior rectus muscle fibrosis. Surgery at the contralateral yoke muscle prevents the risk of overeffect with resulting diplopia in downgaze, which could occur if small distance recession had been performed at the inferior rectus muscle. An overeffect in relation to inferior oblique recession will only cause diplopia in upgaze, which is much less troublesome in daily routine.

[Tumours and metastases of the spine : cavity/coblation surgery and vertebroplasty/kyphoplasty]. / Tumoren und Metastasen an der Wirbelsäule : Cavity/Coblation-Operation und Vertebro-/Kyphoplastie.

BACKGROUND: Radical surgery for metastases in the spine is in many cases not possible, includingthe higher risk of surgery in older patients with co-morbidities. The aims of treatment are: minimally invasive and maximally effective tumour removal, fracture position, stabilization, pain reduction, and improved quality of life. The specific features and problems of diagnosis and treatment using the cavity/coblation method, , the surgical technique, and the results of the treatment of 250 patients with spinal tumours/metastases are presented. MATERIALS AND METHODS: Tumour resection is carried out by plasma field, via percutaneous trans-/extrapedicular access, followed by kyphoplasty. Clinical and radiological follow-up was carried out postoperatively, including data on pain reduction and improvement of quality of life. RESULTS: Within 6 years (March 2008t February 2014) a total of 250 patients, or 812 spines were treated. In 59 cases dorsal percutaneous instrumentation and straightening were carried out. Minimal blood loss and a very low complication rate were recorded. After surgery, significant pain reduction, satisfaction, early mobilization, and improvement in quality of life were demonstrated in all patients. Immediate radio- and chemotherapy could be carried out. In 38 cases cement escaped laterally into the intervertebral space, but this had no clinical relevance. 188 patients have since died because of tumour manifestations. CONCLUSIONS: The cavity/coblation method has been demonstrated to be a safe, minimally invasive procedure, with good short- and long-term results and lower complication rates. A comprehensive diagnostic, including tumour staging, the correct indication, and prognosis estimation, is important.

[Update on endocrine orbitopathy]. / Update endokrine Orbitopathie.

Graves' orbitopathy is an autoimmune disease of the ocular adnex connective tissue and most commonly occurs together with Grave's hyperthyroidism. Anti-TSH receptor antibodies are specific for Graves' disease and are related to both the course of thyroid and orbital diseases. An active inflammatory disease stage is followed by an inactive stage of incomplete remission in most patients. Periorbital swelling, proptosis, diplopia and lid retraction severely impair the patients' quality of life. In the active state anti-inflammatory treatment consists of i.v. steroids, off-label use of immunomodulatory medication, selenium and in emergency cases orbital decompression. Fortunately, defects in inactive stable Graves' orbitopathy can be successfully treated by surgery and involve decompression for proptosis reduction, muscle recession to correct diplopia and (finally) lid surgery.

Bronchoalveolar lavage fluid exosomes contribute to cytokine and leukotriene production in allergic asthma.

BACKGROUND: Leukotrienes (LTs) are potent pro-inflammatory mediators involved in asthma. Exosomes, nanosized vesicles released from various cells, can stimulate or down-regulate immune responses, depending on the state and nature of the originating cell. We have recently shown an altered exosome profile in bronchoalveolar lavage fluid (BALF) of patients with sarcoidosis, but their role in asthma is unknown. Our aims were to investigate whether exosomes from BALF have LT biosynthetic capacity and to explore phenotypic and functional characteristics of BALF exosomes in asthma. METHODS: Bronchoalveolar lavage fluid exosomes were collected from healthy individuals (n = 13) and patients with mild allergic asthma to birch pollen (n = 12) before and after birch allergen provocation. Exosomes were characterized by flow cytometry and Western blot. Their capacity to induce IL-8 and LT production in the human bronchial epithelial cell (BEC) line 16HB14o- was measured by ELISA and reverse-phase HPLC, respectively. RESULTS: Compared to BALF exosomes from healthy individuals, BALF exosomes from asthmatics displayed higher levels of exosome-associated markers, such as the tetraspanins CD63 and CD81 and the scavenger receptor CD36. No major differences were observed between BALF exosomes from before and after allergen provocation. Furthermore, we show that BALF exosomes contain enzymes for LT biosynthesis. The effect of exosomes to promote LTC(4) and IL-8 release in BEC was significantly increased for exosomes from asthmatics, and the CysLT(1) receptor antagonist Montelukast reduced exosome-induced IL-8 secretion. CONCLUSIONS: Bronchoalveolar lavage fluid exosomes from asthmatic and healthy individuals exhibit distinct phenotypes and functions. BALF exosomes from asthmatics might contribute to subclinical inflammation by increasing cytokine and LTC(4) generation in airway epithelium.

[Graves' orbitopaty: inferior rectus tendon elongation for large vertical squint angles that cannot be corrected by simple muscle recession]. / Endokrine Orbitopathie: M.-rectus-inferior-Sehnenverlängerung bei großen vertikalen Schielwinkeln, die nicht durch eine einfache Muskelrücklagerung korrigiert werden können.

BACKGROUND: In motility disorders related to Graves' orbitopathy, recession of fibrotic eye muscles is the treatment of choice. Correction of very large squint angles can be difficult, since the distance of recession is limited by the necessity to maintain a sufficient arc of contact. A new technique of tendon elongation has been developed in order to maintain sufficient arcs of contact even in patients with large horizontal squint angles, especially after orbital decompression surgery. The established dose-effect relationship cannot simply be conveyed to inferior rectus muscle surgery, due to a different impact of simple recession on inferior and medial rectus muscles. METHODS: Recession of the inferior rectus muscle was performed in 10 patients with simultaneous suturing of bovine pericardium (Tutopatch). This procedure was performed as primary surgery in 7 patients (2 after orbital decompression) and as secondary procedure in 3 patients. Squint angle (far distance), bulbus excursion movements and field of binocular single vision were evaluated pre- and postoperatively. RESULTS: Alignment (far distance) was achieved in 8 of 10 cases at the final follow-up examination. Two patients required corrective prisms. Visual fields were virtually free of diplopia in all patients. The dose-response effect for tendon elongation of the inferior rectus muscle was identical to that for the simple recession of this muscle. There were no complications. CONCLUSIONS: The new technique of tendon elongation using a bovine pericardium graft is applicable in large vertical squint angles (with or without prior bony orbital decompression) as well as for corrections after insufficient simple recessions (by realignment of the muscle and secondary suturing of the graft). Functional improvement can thus be achieved through surgery of a single muscle, keeping the other muscles in reserve for further interventions (lowering the risk of postoperative anterior segment ischaemia). There is a dose effect analogous to large horizontal squint angles in Graves' orbitopathy (dosing formula: 1 mm inferior rectus recession [including graft] leads to 2.0° vertical angle reduction). This corresponds to simple recessions of the inferior rectus muscle but differs from tendon elongations of the medial rectus muscles.

[Graves' orbitopathy]. / Endokrine Orbitopathie.

Graves' orbitopathy (GO) is part of an autoimmune systemic disease (prevalence of 0.5 - 2%) which is composed of hyperthyroidism, orbitopathy, dermopathy and acropachy. Stimulating antibodies against the TSH receptor plays the central pathogenetic role and high levels indicate the risk of a severe course of the disease. The main symproms of GO comprise soft tissue inflammation, proptosis impairment of ocular motility and lid retraction. Inflammatory reactions of orbital fibroblasts are responsible for the symptoms. To restrict damage, anti-inflammatory therapy (mainly i. v. systemic steroids, orbital irradiation) is indicated in moderate to severe active disease stages, and surgical orbital decompression is indicated in sight-threatening states. In mild GO selenium administration and otherwise a wait and see strategy is sufficient. In inactive disease stages surgery (orbital decompression, eye muscle surgery and lid surgery) is performed to improve appearance and function. Smoking increases the prevalence and severity of GO and reduces the efficiency of therapy. Restoring euthyroidism leads to an improvement of GO in about 60% of the patients.

Course of pattern-reversed visual evoked cortical potentials in 30 eyes after bony orbital decompression in dysthyroid optic neuropathy.

AIM: To investigate optic nerve function using the pattern-reversed visual evoked cortical potentials (VECP) before and after bony orbital decompression in dysthyroid optic neuropathy (DON) due to Graves' disease. METHODS: A total of 30 eyes of 15 patients (n=14 female) were observed over 30 ± 13 months after bony three-wall orbital decompression. We examined visual acuity (VA), VECP P100 amplitudes and latencies, as well as proptosis using Hertel's exophthalmometry. RESULTS: Mean logarithm of the minimum angle of resolution (logMAR) VA increased, statistically significantly, by 2.4 lines during 30 ± 13 months (from 0.38 ± 0.25 before surgery to 0.14 ± 0.1 at the end of observation, p=0.0001). All eyes maintained or improved vision by at least one line. Mean postoperative reduction of proptosis was 6.4 ± 3 mm. While VECP P100 amplitudes improved significantly, P100 latencies remained abnormal in 18 eyes (60%) during follow-up of 10 ± 7 months. Nine eyes (30%) with previous latency defects improved in at least one check test, five of which normalised completely. Worsening was evident in seven eyes (23%), and three previously normal eyes developed new pathological latencies. P100 latencies in 14 eyes (47%) remained unchanged. CONCLUSION: After decompression surgery, DON remission was observed in all patients regarding vision and VECP amplitudes. New or persistent P100 latency defects were seen in 60% of eyes after surgery. DON is considered to be caused by compressive ischaemic damage, which further underlines the importance of early decompression surgery.

[Graves' ophthalmopathy]. / Endokrine Orbitopathie.

Graves' orbitopathy is part of an autoimmune systemic disease which compiles hyperthyroidism, orbitopathy, dermopathy and acropachy. Stimulating antibodies against the TSH receptor play the central pathogenetic role. Main symptoms of Graves' orbitopathy comprise soft tissue inflammation, proptosis impairment of ocular motility and lid retraction. Inflammatory reactions of orbital fibroblasts are responsible for the symptoms. To restrict damage anti-inflammatory therapy (mainly systemic steroids, orbital irradiation) is indicated in moderate to severe active disease stages, and surgical orbital decompression in sight threatening states. In mild cases expectant strategy and selenium administration is sufficient. In inactive disease stages surgery is performed to improve appearance and function. Restoring euthyroidism leads to improvement of Graves' orbitopathy in about 60% of the patients. Radioiodine therapy without glucocorticoids is associated with a small but significant risk (15%) of deterioration or relapse. Thyroidectomy is neutral in later stages but may improve Graves' orbitopathy in early active stages.

[Eye muscle surgery in unilateral abducens palsy]. / Augenmuskelchirurgie bei einseitiger Abduzensparese.

BACKGROUND: As there are only few data on squint angle reduction following surgical treatment of unilateral abducens palsy, we aimed to quantify squint angle reduction after several different surgical procedures. PATIENTS AND METHODS: Retrospective analysis of 88 consecutive files of patients with unilateral abducens palsy, treated in 2000 - 2007 (46 resections of the lateral rectus muscle, 25 resections of the lateral rectus combined with recession of the medial rectus, 17 Hummelsheim transpositions, modified by Kaufmann). Maximal abduction was possible up to primary position in all 17 patients with Hummelsheim transposition. All other patients (except two) were able to abduct beyond primary position. RESULTS: In resections of the lateral rectus a stable dose-effect-correlation was found: the dose-effect coefficients (DEC) ranged between 1.5 degrees and 1.6 degrees reduction of horizontal angle (far fixation)/mm of resected muscle. In combined convergence procedures the DEC ranged from 1.52 degrees /mm (7-9 mm recession/resection) up to 1.39 degrees /mm (13-15 mm recession/resection). In muscle transpositions (Hummelsheim-Kaufmann), preoperative horizontal squint angle (far distance) was reduced from +29 degrees (median, range +15 degrees to +50 degrees ) to -3 degrees (median, range -15 degrees to +17 degrees ) postoperatively (6-8 weeks). The best results were achieved with preoperative squint angels between > +20 degrees and < +35 degrees . Larger basic angles showed mostly undercorrection; smaller angles showed always overcorrection. CONCLUSIONS: Unilateral abducens palsy with maximal abduction up to primary position should be treated by muscle transposition. With squint angles (far distance) < +20 degrees a classical Hummelsheim transposition is recommended, with squint angles > +20 degrees the Kaufmann's modification should be preferred. If abduction beyond primary position is possible, lateral rectus resection suffices. With squint angles > +12 degrees additional recession of the ipsilateral medial rectus muscle becomes necessary.