The CDK Inhibitor Dinaciclib Improves Cisplatin Response in Nonseminomatous Testicular Cancer: A Preclinical Study.

BACKGROUND: Most patients with testicular germ cell tumors (GCTs) are treated with cisplatin (CP)-based chemotherapy. However, some of them may develop CP resistance and therefore represent a clinical challenge. Cyclin-dependent kinase 5 (CDK5) is involved in chemotherapy resistance in different types of cancer. Here, we investigated the possible role of CDK5 and other CDKs targeted by dinaciclib in nonseminoma cell models (both CP-sensitive and CP-resistant), evaluating the potential of the CDK inhibitor dinaciclib as a single/combined agent for the treatment of advanced/metastatic testicular cancer (TC). METHODS: The effects of dinaciclib and CP on sensitive and resistant NT2/D1 and NCCIT cell viability and proliferation were evaluated using MTT assays and direct count methods. Flow cytometry cell-cycle analysis was performed. The protein expression was assessed via Western blotting. The in vivo experiments were conducted in zebrafish embryos xenografted with TC cells. RESULTS: Among all the CDKs analyzed, CDK5 protein expression was significantly higher in CP-resistant models. Dinaciclib reduced the cell viability and proliferation in each cell model, inducing changes in cell-cycle distribution. In drug combination experiments, dinaciclib enhances the CP effect both in vitro and in the zebrafish model. CONCLUSIONS: Dinaciclib, when combined with CP, could be useful for improving nonseminoma TC response to CP.

Clinical evaluation of tear substitute utility after anti-VEGF intravitreal injection.

PURPOSE: The purpose of this study is to evaluate the role of a polyethylene glycol 400 - propylene glycol - hydroxypropyl guar - hyaluronic acid eye drops in relieving the symptoms of dry eye syndrome after anti-VEGF intravitreal injection. METHODS: In this randomized, parallel-group study, patients were randomized to receive standard therapy alone or study eye drops plus standard therapy. Patients enrolled were older than 50 with exudative age-related macular degeneration, who have never had intravitreal injections, and without severe dry eye condition or severe ocular or systemic conditions. Patients had baseline preoperative evaluation (V0), and successively after 15 (V1) and 30 (V2) days. At VO and V1 T-BUT, Schirmer's test, fluorescein staining, DEQ5 and OSDI questionnaires were performed and at V2 (30) the OSDI questionnaire was administered. RESULTS: 80 patients were included in the study, of them 40 received standard therapy plus study eye drops. DEQ5 questionnaire showed an increase in the control group between the values at V0 and V1, while in the study group a decrease was observed. No changes in T-BUT, Schirmer, and fluorescein staining values between V0 and V1 were observed in both groups. OSDI data in the control group showed no statistically significant differences, while in the study group they showed a statistically significant difference. CONCLUSIONS: In our study patients undergoing for the first time intravitreal treatment presented dry eye symptoms in the postoperative period: in this group of patients the use of a tears substitute reduces postoperative ocular discomfort.

Cisplatin Cytotoxicity in Human Testicular Germ Cell Tumor Cell Lines Is Enhanced by the CDK4/6 Inhibitor Palbociclib.

BACKGROUND: Cisplatin-based chemotherapy is the mainstay of pharmacological treatment of testicular germ cell tumors (TGCTs) that, together with early diagnosis, surgery, and/or radiotherapy, has dramatically improved the prognosis. However, under the pressure of such pharmacological therapy (both classical cytotoxic drugs and targeted therapy), cancer cells may develop resistance. Thus, combination therapy that may include cytotoxic drugs and targeted therapy could offer an advantage to curing cancers. Here, we investigated the in vitro and in vivo antitumor activity of cisplatin, as a single-agent or in combination with palbociclib. PATIENTS AND METHODS: The cell viability of Ntera-2/cl.D1 (NT2/D1) and 833K after exposure to palbociclib and/or cisplatin was evaluated by MTT dye reduction assay and by ATPLite Luminescence Assay. Gene and protein expression was evaluated by quantitative reverse transcription polymerase chain reaction and by western blot. Flow cytometric cell-cycle analysis was performed, as well. The in vivo experiments were conducted on NT2/D1 xenografts in AB zebrafish embryos exposed to the drugs. RESULTS: Palbociclib and cisplatin decreased TGCT cell viability both in vitro and in vivo. This effect was additive when cells were exposed to the drug combination. In the NT2/D1 cell lines, the drug combination also exerted a positive effect with regard to delaying cell recovery after the toxic insult. In the combination experiments, cisplatin-induced cell accumulation in G2/M was predominant compared with the palbociclib effect. CONCLUSIONS: These results could provide the rationale for developing further studies to improve the pharmacological treatment of TGCTs, but they must be demonstrated in a dedicated clinical trial.

Applicability of COVID-19 Pandemic Recommendations for Urology Practice: Data from Three Major Italian Hot Spots (BreBeMi).

BACKGROUND: Lombardy has been the first and one of the most affected European regions during the first and second waves of the novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]). OBJECTIVE: To evaluate the impact of coronavirus disease 2019 (COVID-19) on all urologic activities over a 17-wk period in the three largest public hospitals in Lombardy located in the worst hit area in Italy, and to assess the applicability of the authorities' recommendations provided for reorganising urology practice. DESIGN SETTING AND PARTICIPANTS: A retrospective analysis of all urologic activities performed at three major public hospitals in Lombardy (Brescia, Bergamo, and Milan), from January 1 to April 28, 2020, was performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Join-point regression was used to identify significant changes in trends for all urologic activities. Average weekly percentage changes (AWPCs) were estimated to summarise linear trends. Uro-oncologic surgeries performed during the pandemic were tabulated and stratified according to the first preliminary recommendations by Stensland et al (Stensland KD, Morgan TM, Moinzadeh A, et al. Considerations in the triage of urologic surgeries during the COVID-19 pandemic. Eur Urol 2020;77:663-6) and according to the level of priority recommended by European Association of Urology guidelines. RESULTS AND LIMITATIONS: The trend for 2020 urologic activities decreased constantly from weeks 8-9 up to weeks 11-13 (AWPC range -41%, -29.9%; p < 0.001). One-third of uro-oncologic surgeries performed were treatments that could have been postponed, according to the preliminary urologic recommendations. High applicability to recommendations was observed for non-muscle-invasive bladder cancer (NMIBC) patients with intermediate/emergency level of priority, penile and testicular cancer patients, and upper tract urothelial cell carcinoma (UTUC) and renal cell carcinoma (RCC) patients with intermediate level of priority. Low applicability was observed for NMIBC patients with low/high level of priority, UTUC patients with high level of priority, prostate cancer patients with intermediate/high level of priority, and RCC patients with low level of priority. CONCLUSIONS: During COVID-19, we found a reduction in all urologic activities. High-priority surgeries and timing of treatment recommended by the authorities require adaptation according to hospital resources and local incidence. PATIENT SUMMARY: We assessed the urologic surgeries that were privileged during the first wave of coronavirus disease 2019 (COVID-19) in the three largest public hospitals in Lombardy, worst hit by the pandemic, to evaluate whether high-priority surgeries and timing of treatment recommended by the authorities are applicable. Pandemic recommendations provided by experts should be tailored according to hospital capacity and different levels of the pandemic.

A thigh urinary fistula following radical prostatectomy and external beam radiation therapy for prostate cancer: a case report.

Urinary fistula is a rare but severe complication which could occur after radiation therapy for prostate cancer (PCa). We describe the case of an inner thigh urinary fistula in a patient treated with radical prostatectomy and adjuvant radiation therapy for PCa. A 76-year-old man presented to the emergency room complaining of right thigh swelling, pain and fever. Computed tomography scan and urethra-cystography showed bladder-neck leakage and fluid collection, extended from the pelvis to the right inner thigh. Patient was treated with ultrasound-guided drainage and intravenous antibiotics. Timely diagnosis and treatment are necessary in order to reduce possible evolution to necrotizing fasciitis.

Standard vs delayed ligature of the dorsal vascular complex during robot-assisted radical prostatectomy: results from a randomized controlled trial.

PURPOSE: Prospective randomized trial to compare standard vs delayed approach to dorsal vascular complex (s-DVC vs d-DVC) in robot-assisted radical prostatectomy (RARP). METHODS: Patients scheduled for RARP were randomized into a 1:1 ratio to receive either s-DVC or d-DVC by two experienced surgeons. In s-DVC arm an eight-shaped single stitch was given at the beginning of the procedure and the DVC was subsequently cut at time of apical dissection; in d-DVC arm the plexus was transected at the end of prostatectomy, prior to apex dissection and then sutured. Primary endpoint was difference in estimated blood loss (EBL) and a sample size of 226 cases was calculated; ad interim analysis was planned after 2/3 of recruitment. RESULTS: Endpoint was reached at ad interim analysis after 162 cases (81 s-DVC, 81 d-DVC) and recruitment was, therefore, interrupted. Baseline and tumor characteristics were overlapping. EBL was significantly higher in d-DVC arm (mean EBL 107 vs 65 ml, p = 0.003), but without differences in post-operative hemoglobin, transfusions and complications. Overall PSM rate was higher in d-DVC arm (21.0 vs 14.8%, p = 0.323), with statistical significance relatively to organ-confined disease (15.5 vs 3.6%, p = 0.031). Apical involvement was instead significantly higher in s-DVC arm (prevalence in PSM patients 66.7 vs 23.5%, p = 0.020). Post-operative PSA, continence and potency rates were similar between groups. CONCLUSIONS: Standard and delayed approaches to DVC are safe and lead to similar functional outcomes. A delayed approach exposes to a higher risk of PSM in organ-confined disease but with a lower risk of apical involvement.

Holographic Reconstructions for Preoperative Planning before Partial Nephrectomy: A Head-to-Head Comparison with Standard CT Scan.

BACKGROUND: Preoperative surgical planning before partial nephrectomy (PN) is a time-consuming and fragmentary process. OBJECTIVES: To evaluate the differences in the perception of renal anatomy between holographic reconstruction (HR) versus computed tomography (CT) in patients who are candidate to PN. METHODS: CT scans of 10 consecutive patients with intermediate/high complexity renal masses (R.E.N.A.L. score > 8) scheduled for robot-assisted PN were translated into HR. Seven raters independently described how they interpreted several anatomical details from CT and HR respectively. The exams were presented unpaired and randomly. Inter-observer agreement and evaluation time were assessed. A questionnaire inquired clinical utility of CT and HR. Inter-observer agreement was measured by the Cohen's kappa test. Evaluation time for CT and HR was compared by the Kruskal-Wallis test, overall and per rater. Examiners answered to the questionnaire following a Likert scale. RESULTS: HR showed a higher inter-observer agreement, reaching a good level (k > 0.6) for almost all the anatomical details considered. Conversely, CT generally provided a fair or poor agreement (k < 0.6). The evaluation time was shorter for HR (mean 1.7 vs. 3.4 min, p < 0.0001). All raters declared that HR could facilitate preoperative planning before PN. CONCLUSIONS: HR can be useful for preoperative surgical planning before PN to ease the understanding of anatomy.

Measuring recovery of visual function in children with papilledema using sweep visual evoked potentials.

PURPOSE: To assess visual function in children with papilledema using sweep visual evoked potentials (VEP) to determine whether vision function improved following treatment. METHODS: Contrast sensitivity and grating acuity were prospectively measured by using sweep visual evoked potential testing in children with mild or moderate acute papilledema. A subset of children were tested longitudinally before and after treatment. Subject data was compared with that of age-matched controls using the Wilcoxon-Mann-Whitney test. RESULTS: A total of 9 subjects (age range, 9-16 years) and 11 controls were included; 5 subjects were studied longitudinally. The control group's logMAR grating acuity (mean, 0.09; range, -0.13 to 0.36) was better than that of the papilledema group (mean, 0.36; range 0.15-0.59). Four patients showed recovery of contrast sensitivity following treatment of their raised intracranial pressure between first and last visit. CONCLUSIONS: In our study cohort, sweep VEP was able to detect early improvement in contrast sensitivity despite absence of apparent clinical change in disk edema in children undergoing treatment for raised intracranial pressure.

Visual development of human milk-fed preterm infants provided with extra energy and nutrients after hospital discharge.

BACKGROUND: Human milk (HM) is the optimal way to nourish preterm low birth weight (LBW) infants after hospital discharge. However, there are few data on which to assess whether HM alone is sufficient to address hospital-acquired nutrition deficits, and no adequately powered studies have examined this question using neurodevelopment as an outcome. The purpose of this work was to determine whether adding extra energy and nutrients to the feedings of predominantly HM-fed LBW infants early after discharge improves their visual development. Visual development was used in this study as a surrogate marker for neurodevelopment. METHODS: At discharge, 39 predominantly HM-fed LBW infants (750-1800 g, 1288 ± 288 g) were randomized to receive human milk alone (control) or around half of the HM received daily mixed with a multinutrient fortifier (intervention) for 12 weeks. Grating acuity (ie, visual acuity) and contrast sensitivity were assessed using sweep visual-evoked potential tests at 4 and 6 months corrected age. RESULTS: At 4 and 6 months corrected age, intervention infants demonstrated higher grating acuity compared to those in the control group (intervention: 7.8 ± 1.3 and 9.7 ± 1.2 [cycles/degree] vs control 6.9 ± 1.2 and 8.2 ± 1.3, P = .02). Differences in contrast sensitivity did not reach statistical significance (P = .11). CONCLUSION: Adding a multinutrient fortifier to a portion of the expressed breast milk provided to predominantly HM-fed LBW infants early after discharge improves their early visual development. Whether these subtle differences in visual development apply to other aspects of development or longer term neurodevelopment are worthy of future investigation.

[High-intensity focused ultrasound (HIFU): our experience in the treatment of prostate cancer relapsing after radiotherapy]. / Ultrasuoni focalizzati ad alta intensità (HIFU): la nostra esperienza nel trattamento del carcinoma prostatico recidivo a radioterapia.

The aim of the study is to evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) treatment in patients with local prostate cancer recurrence after radiotherapy. From February 2009 to June 2010, 14 patients with prostate cancer recurrence after radiotherapy were selected for HIFU treatment; all patients had a positive TRUS-guided biopsy and the absence of distant metastases was confirmed by computer tomography, PET choline or bone scintigraphy. We classified all patients in 3 groups using D'Amico's classification: 4 patients high risk (PSA >20 ng/ml - 8≤ Gleason Score≤ 10 - clinical stage≥T2c), 8 patients intermediate risk (10 PSAnadir+1.2ng/ml) or after adjuvant therapy introduction. All complications were recorded. Of the 14 patients selected, 12 patients underwent HIFU treatments; 2 patients were excluded because of rectal strictures induced by radiotherapy. At a mean 13 months' follow-up, biochemical success rate was obtained in 1 of the high risk patients and in 5 of the low and intermediate risk patients; 1 man died for a disease not correlated with prostate cancer recurrence. Complications included urinary tract infection, acute urinary retentions, urethral strictures and light stress incontinence. In our experience salvage HIFU is a safe treatment option for local relapse after radiotherapy; its efficacy depends on a careful patient selection.

Deficits in perception of images of real-world scenes in patients with a history of amblyopia.

OBJECTIVES: To investigate the perception of images of real-world scenes in patients with amblyopia and to compare their performance with that of visually normal participants by viewing conditions (monocular vs binocular) and by treatment outcomes (successfully vs unsuccessfully treated vs normal eyes). METHODS: Thirty-nine healthy and 26 amblyopic individuals who had undergone previous amblyopia treatment were recruited to perform a match-to-sample task that used images of real-world scenes. Rates of correct, incorrect, and no responses and mean reaction time were recorded. RESULTS: Performance during monocular viewing showed that the mean correct response rate was 59% in the amblyopic eyes, 62% in the fellow eyes, and 67% in the normal eyes (P = .008). During binocular viewing, the correct response rate remained reduced at 58% in amblyopic patients compared with 68% in participants with normal vision (P = .03). Performance by treatment outcomes showed that the mean correct response rate was 59% in the unsuccessfully treated group, 64% in the successfully treated group, and 67% in the normal group (P = .002). There was no difference in performance among amblyopia subtypes. CONCLUSIONS: Real-world scene perception is impaired in amblyopia, with the poorest performance during amblyopic monocular and binocular viewing. Despite successful treatment of the amblyopic eye to normal acuity levels, perception of images in real-world scenes remains deficient in patients with a history of amblyopia.

[Hydronephrosis caused by inferior vena cava penetration by a mobin-uddin filter]. / Idroureteronefrosi secondaria a perforazione della parete della vena cava inferiore da parte di filtro cavale.

The inferior vena cava (IVC) filter placement represents an excellent protection from significant pulmonary embolism in at-risk patients. Perforation of the wall of the IVC by components of caval filters is a recognized complication. We report a case of asymptomatic hydronephrosis caused by transcaval penetration of a Mobin-Uddin filter.

Effects of earth-fixed vs head-fixed targets on static ocular counterroll.

OBJECTIVE: To investigate whether static ocular counterroll (OCR) gain is reduced during viewing of an earth-fixed vs a head-fixed target. METHODS: Twelve healthy individuals were recruited. The target consisted of a red fixation cross against a grid pattern at a viewing distance of 33 cm. The target was mounted on a wall (earth fixed) or was coupled to the head (head fixed). Changes in mean torsional eye position were plotted as a function of head position steps (0 degrees +/- 25 degrees in 5 degrees steps), and sigmoidal fits were performed. Mean static OCR gain was calculated by taking the derivative of the fitted functions. RESULTS: Mean static OCR gain was 40% lower with a head-fixed target (-0.084) than with an earth-fixed target (-0.141) (P < .001). CONCLUSION: The reduction in static OCR gain during viewing of a head-fixed target indicates that static OCR is partially negated when a target moves with the head.

Effectiveness of telescopic magnification in the treatment of amblyopia: a pilot study.

OBJECTIVE: To compare the effectiveness of patching plus telescopic magnification vs patching alone in treating refractory amblyopia. METHODS: Children aged 4 to 17 years who failed previous amblyopia treatment were recruited into this prospective study. Subjects were randomly assigned to either 30 minutes per day of patching of the fellow eye only (n = 7) or 30 minutes per day of patching of the fellow eye plus concurrent use of a telescope in the amblyopic eye (n = 8). MAIN OUTCOME MEASURE: Best-corrected logMAR visual acuity score of the amblyopic eye after 17 weeks of treatment. RESULTS: Both treatment groups demonstrated significant improvement in visual acuity in the amblyopic eye after 17 weeks (P = .001). Improvements in the patching-only group were slightly greater over the course of treatment, but this difference was not statistically significant (P = .06). At 17 weeks, mean visual acuity improvement from baseline was 0.14 logMAR (SD, 0.13 logMAR) in the patching-only group and 0.06 logMAR (SD, 0.17 logMAR) in the patching plus telescope group (P = .11). The 17-week visual acuity was at least 0.2 logMAR and/or improved from baseline by at least 0.2 logMAR in 2 patients in the patching-only group and none in the patching plus telescope group (P = .08). CONCLUSION: Treatment of refractory amblyopia in children using telescopic magnification did not appear to confer any additional benefits over patching alone. APPLICATION TO CLINICAL PRACTICE: Occlusion and penalization remain the standard of care for patients with amblyopia and should remain the benchmark against which other treatments are compared in clinical trials for amblyopia therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00970554.

Effects of age, viewing distance and target complexity on static ocular counterroll.

The ocular counterroll (OCR) reflex generates partially compensatory torsional eye movements during static head roll tilt. We assessed the influence of age, viewing distance and target complexity on the OCR across the age span (13-63 years; n=47), by recording eye movements during head-on-body roll tilt (0+/-40 degrees in 5 degrees steps) while subjects viewed simple vs. complex targets at 0.33 and 1m. We found that subjects > or = 31 years had lower gains than those < or =30 years, but only for far targets. Consistent with prior reports, far targets elicited higher OCR gains than near targets, and target complexity had no effect on gains, suggesting that visual input is primarily used to maintain vergence during OCR.

Reduced grating acuity associated with retinal toxicity in children with infantile spasms on vigabatrin therapy.

PURPOSE: To determine whether visual functions are decreased in children with infantile spasms and vigabatrin-attributed retinal toxicity. METHODS: Contrast sensitivity and grating acuity were measured by using sweep visual evoked potential (VEP) testing in 42 children with infantile spasms (mean age, 29.23 +/- 18.31 months). All children had been exposed to vigabatrin (VGB) for a minimum of 1 month. These children were divided into retinal toxicity and no toxicity groupings based on 30-Hz flicker amplitude reductions on the full-field electroretinogram. A multivariate analysis of variance (MANOVA) compared visual functions between children with and without retinal toxicity. RESULTS: The MANOVA showed that visual function was significantly affected by VGB retinal toxicity. Further univariate analysis revealed that grating acuity was significantly reduced in children with toxicity. No differences in contrast sensitivity were found between children with toxicity and those without. CONCLUSIONS: Reduced visual functions from VGB-attributed retinal toxicity can be detected in children with infantile spasms with the sweep VEP.

The linear vestibulo-ocular reflex in patients with skew deviation.

PURPOSE: The linear vestibulo-ocular reflex (LVOR) is mediated primarily by the otolith organs in the inner ear. Skew deviation is a vertical strabismus believed to be caused by imbalance of otolithic projections to ocular motor neurons (disynaptically through the medial longitudinal fasciculus in the brain stem or polysynaptically through the cerebellum). The authors postulated that if skew deviation is indeed caused by damage to these projections, patients with skew deviation would show abnormal LVOR responses. METHODS: Six patients with skew deviation caused by brain stem or cerebellar lesions and 10 healthy subjects were recruited. All subjects underwent brief, sudden, interaural translations of the head (head heaves) using a head-sled device at an average peak acceleration of 0.42g (range, 0.1-1.1g) while continuously viewing an earth-fixed target monocularly at 15 and 20 cm. LVOR sensitivity (peak rotational eye velocity to peak linear head velocity) and velocity gain (peak actual-to-ideal rotational eye velocities) were calculated for the responses within the first 100 ms after onset of head movements. RESULTS: LVOR sensitivities and velocity gains in patients were decreased by 56% to 62% in both eyes compared with healthy subjects. This binocular reduction in LVOR responses was asymmetric--the magnitude of reduction differed between eyes by 37% to 143% for sensitivities and by 36% to 94% for velocity gains. There were no differences in response between right and left heaves. CONCLUSIONS: The binocular, asymmetric reduction in LVOR sensitivity and velocity gain provides support that imbalance in the otolith-ocular pathway is a mechanism of skew deviation.

Neural correlates of transformational apparent motion.

Transformational apparent motion (TAM) arises when a shape that is abruptly flashed on and off next to a static shape of similar color or texture appears as a protrusion that extends and retracts smoothly from the static object. Here we report that the strength of the TAM percept can be predicted from the waveform of visual evoked potentials (VEPs) measured while observers rated their percepts. The VEPs at pattern onset and offset are maximally symmetric when the static inducer and the flashing patches of the display are of the same contrast. VEP symmetry is affected by how the two patches can be matched as a single surface and may reflect the relative contribution of different motion and object detection systems in visual cortex.

Predictors of postacute mortality following traumatic brain injury in a seriously injured population.

BACKGROUND: Traumatic brain injury (TBI) is a primary cause of injury mortality in developed countries but less is known about the impact of TBI on postacute mortality in large study populations. This study investigates the rate and predictors of postacute mortality (1-9 years after the initial injury) of severely injured persons with TBI in the Province of Ontario from April 1, 1993 to March 31, 1995. METHOD: Cases were identified (n = 2,721) from the Ontario Trauma Registry Comprehensive Data Set based on lead trauma hospitals in the province which also provided data on predictors. Severely injured patients (n = 557) who had lower extremity injuries during the sample time period formed a control population. RESULTS: Poisson regression modeling showed that having a TBI was a significant predictor of premature death controlling for age and injury severity. Age, the number of comorbidities, injury severity, mechanism of injury, and discharge destination were significant predictors in the multivariate analyses for the TBI population. CONCLUSIONS: This research quantifies the elevated risk of premature death in the postacute period for seriously injured adults with TBI and identifies factors most associated with highest mortality rates in this population.

Timing of surgery for infantile esotropia in humans: effects on cortical motion visual evoked responses.

PURPOSE: Infantile esotropia is associated with maldevelopment of cortical visual motion processing, manifested as directional asymmetry of motion visual evoked potentials (mVEPs). The purpose of this study was to determine whether early surgery at or before age 11 months could promote the development of cortical visual motion processing in human infants, compared with standard surgery at age 11 to 18 months. METHODS: Sixteen children with a constant, infantile esotropia >or=30 prism diopters and onset before age 6 months were recruited prospectively. Eight of them underwent early surgery at