Proof-of-concept and Randomized, Placebo-controlled Trials of an FcRn Inhibitor, Batoclimab, for Thyroid Eye Disease.

CONTEXT: Inhibition of the neonatal fragment crystallizable receptor (FcRn) reduces pathogenic thyrotropin receptor antibodies (TSH-R-Ab) that drive pathology in thyroid eye disease (TED). OBJECTIVE: We report the first clinical studies of an FcRn inhibitor, batoclimab, in TED. DESIGN: Proof-of-concept (POC) and randomized, double-blind placebo-controlled trials. SETTING: Multicenter. PARTICIPANTS: Patients with moderate-to-severe, active TED. INTERVENTION: In the POC trial, patients received weekly subcutaneous injections of batoclimab 680 mg for 2 weeks, followed by 340 mg for 4 weeks. In the double-blind trial, patients were randomized 2:2:1:2 to weekly batoclimab (680 mg, 340 mg, 255 mg) or placebo for 12 weeks. MAIN OUTCOME: Change from baseline in serum anti-TSH-R-Ab and total IgG (POC); 12-week proptosis response (randomized trial). RESULTS: The randomized trial was terminated because of an unanticipated increase in serum cholesterol; therefore, data from 65 of the planned 77 patients were analyzed. Both trials showed marked decreases in pathogenic anti-TSH-R-Ab and total IgG serum levels (P < .001) with batoclimab. In the randomized trial, there was no statistically significant difference with batoclimab vs placebo in proptosis response at 12 weeks, although significant differences were observed at several earlier timepoints. In addition, orbital muscle volume decreased (P < .03) at 12 weeks, whereas quality of life (appearance subscale) improved (P < .03) at 19 weeks in the 680-mg group. Batoclimab was generally well tolerated, with albumin reductions and increases in lipids that reversed upon discontinuation. CONCLUSIONS: These results provide insight into the efficacy and safety of batoclimab and support its further investigation as a potential therapy for TED.

Imaging of the medial rectus muscle predicts the development of optic neuropathy in thyroid eye disease.

Goal of the study was to evaluate bony orbit remodeling and extraocular muscle (EOM) volume in thyroid eye disease (TED) and their role as predicting factors for development of dysthyroid optic neuropathy (DON). Orbital computed tomography of 92 patients with TED with (76 orbits) or without DON (98 orbits) were retrospectively evaluated. Orbits (n = 40) of subjects without TED served as controls. Measurements of the bony orbit as well as EOM volume were incorporated into a generalized linear mixed model to predict DON. The angle of the medial orbital wall was significantly smaller (p < 0.001) in patients with TED (- 2.3 ± 3.6°) compared to patients with TED + DON (1.0 ± 4.1°). Both groups differed significantly from controls (- 4.2 ± 2.7°). Bowing of the medial orbital wall correlated positively with muscle volume (r = 0.564; p < 0.001). Total EOM volume was significantly larger in TED + DON (7.6 ± 2.5cm3) compared to TED only (5.6 ± 3.0cm3; p < 0.001) or controls (2.6 ± 0.5cm3). Multivariate analysis revealed the medial rectus muscle volume (TED: 1.06 ± 0.48cm3 vs. TED + DON: 2.16 ± 0.84cm3) as the strongest predictor, achieving a specifity of 86.7% and a sensitivity of 73.7% in diagnosing DON in univariate analysis. Though characterized by a wide range of variability, increased medial rectus muscle volume is the strongest predictor for DON in our patient cohort with TED when analyzing a single muscle.

Sinogenic Orbital Complications.

BACKGROUND: The term "orbital complication" does not designate an independent nosological entity, but is rather a collective designation for diseases or disease effects that involve the orbit and its internal structures by extension from outside. In general, their most prominent manifestation is swelling of the orbital soft tissues, usually unilaterally. The incidence of sinogenic orbital complications is approximately 1.6 per 100 000 children and 0.1 per 100 000 adults per year. METHODS: This review is based on publications retrieved by a selective search of the literature on the epidemiology, diagnosis, and treatment of sinogenic orbital complications. RESULTS: Acute sinusitis is the most common cause of orbital complications. These are diseases of the orbit with potentially serious consequences for the eye and the risk of intracranial complications such as cavernous sinus thrombosis, meningitis, or brain abscess. Aside from acute sinusitis, many other infectious and non-infectious diseases can extend to and involve the orbit. Because of the complexity and severity of the condition, its diagnosis and treatment are always an interdisciplinary matter. The treatment is primarily conservative, under observation in a hospital, and generally consists of the treatment of acute sinusitis with measures to combat edema along with the administration of broad-spectrum antibiotics. Surgical intervention is needed in severe cases or if there is an abscess. An endonasal approach is usually used for drainage. CONCLUSION: In 95-98% of cases in stages I-IV, healing is complete and without further sequelae. Even if vision is affected preoperatively, it usually recovers fully when therapy is appropriate. Approximately 15% of the patients who undergo surgery need more than one operative procedure.

Retinal thinning in phenylketonuria and Gaucher disease type 3.

PURPOSE: Retinal alterations in inherited metabolic diseases associated with neurodegeneration are poorly studied. The objective was to study retinal thickness, specifically the components of the ganglion cell complex (GCC)-nerve fiber layer (NFL), ganglion cell layer (GCL), and inner plexiform layer (IPL)-using spectral-domain optical coherence tomography (SD-OCT) in two different diseases with potential dopaminergic depletion, phenylketonuria (PKU) and Gaucher disease type 3 (GD3). METHODS: Retinal layers in 19 patients with PKU, 15 patients with GD3, and 93 healthy individuals were measured using peripapillary ring scan and macular SD-OCT. Linear mixed models were computed including an adjustment for age, sex, and spherical equivalent. We calculated Spearman's rank correlations between retinal layer measurements and clinical and/or laboratory parameters. RESULTS: Thinning of total retinal thickness was found in the macular inner ring (p = 0.002), and outer ring (p = 0.012), sparing the fovea (p = 0.12) in PKU, while in GD3, all subfields were thinned (fovea p < 0.001, inner ring p = 0.047, outer ring 0.07). In both conditions, thinning was most evident in the NFL, GCL, and IPL, while OPL (outer plexiform layer) was thickened. Peripapillary retinal nerve fiber layer measurements remained normal. GCL and IPL in PKU correlated with tyrosine serum concentration. CONCLUSION: Thinning of the NFL, GCL, and IPL, with thickened OPL, are both found in PKU and in GD3. Low dopamine concentrations in the retina might promote these effects. However, these data do not give evidence that retinal measurements can be used as a biomarker for disease severity in patients with GD3.

[IgG4-related disease]. / IgG4-assoziierte Erkrankung.

BACKGROUND: The IgG4-related systemic disease as well as the homonymous variant IgG4-related orbital disease were first described less than 15 years ago. The mostly subacute clinical symptoms can be multifarious and the classical case is characterized by an orbital inflammatory condition with a bilateral enlargement of the lacrimal glands; however, any other orbital tissue with the exception of the eyeball can be affected by the lymphocytic inflammatory infiltration. MATERIAL AND METHODS: Based on the current literature the clinical picture, epidemiology, pathogenesis and treatment options are described. A focus is on the differential diagnostic demarcation from other inflammatory processes of the orbit. CONCLUSION: The IgG4-related orbital disease is an important differential diagnosis of inflammatory diseases of the orbit. The condition can exhibit considerable clinical and imaging similarity to idiopathic inflammation of the orbit, to the specific inflammations seen in systemic diseases, to Graves' orbitopathy and to lymphoproliferative diseases and lymphoma. After histopathologic confirmation the interdisciplinary clarification and treatment consensus are indispensable.

Vertical saccadic palsy and foveal retinal thinning in Niemann-Pick disease type C.

INTRODUCTION: Niemann-Pick type C (NPC) is a lysosomal storage disease that is progressive and life-limiting, with an estimated incidence of 1:120,000 live births. In addition to systemic manifestation with (hepato-)splenomegaly, there are a number of neurological manifestations (ataxia, dysarthria, dementia, cataplexy, epileptic seizures, and psychiatric disorders). Characteristic is vertical supranuclear gaze palsy, which is often overlooked. Early diagnosis and start of therapy improve quality of life. This study aimed to characterize oculomotor dysfunction of NPC patients, and to provide ophthalmologic data including retinal imaging. METHODS: Eighteen patients with biochemically or genetically diagnosed NPC completed oculomotor and ophthalmologic examination. Ten of them performed saccadometry by infrared based video-oculography. Saccadic parameters were compared to 100 healthy controls, and were correlated with clinical variables. Another subgroup of eight patients received optical coherence tomography (OCT) of the optic disc and the macula, of which the segmented layers were analysed using a crude linear mixed model, and one adjusted for age, sex, and spherical equivalent. RESULTS: Saccadometry revealed slowed peak velocity compared to controls most evident vertically. Peak velocity correlated negatively with SARA-Score, but correlation with clinical assessment of saccades was not significant. Clinical features in the assessment of vertical saccades were intensive blinking and head movements to initiate gaze changes, and lateral trajectory of the eyes. Macular OCT revealed significant total retinal thinning in the fovea, specifically of the outer nuclear layer and outer retinal layer. Para- and perifoveal retinal thicknesses, as well as peripapillary retinal nerve fibre layer were normal. CONCLUSIONS: Foveal thinning was revealed in NPC. It remains to be shown, whether OCT will prove to be useful to monitor progression. Saccadic impairment reflects CNS involvement and therefore is a parameter to demonstrate the progression of NPC, and potentially also the efficacy of new therapies. Saccadometry, in contrast to clinical investigation, allows the precise evaluation of saccades.

[Visual acuity in German preschool children-results of a cross-sectional study]. / Wie gut sehen unsere ABC-Schützen?

BACKGROUND: Within the framework of the German pediatric screening examinations, the checks include visual functions. There is no ophthalmological screening examination in childhood in Germany. This study investigated whether participation in the pediatric screening examinations U8 (at the end of the fourth year of life) and U9 (at the beginning of the sixth year of life) is associated with the results of visual acuity, which are compiled at the school entry examinations (SEU). METHODS: This study evaluated data of the SEU for school the enrollment years 2009/2010-2014/2015 of the State of Rhineland-Palatinate. In these years visual acuity was assessed using the Rodenstock visual testing device (E-hooks; Rodenstock intruments GmbH, Ottobrunn, Deutschland) wearing glasses if present. The association between participation in the U8 and U9 screening examinations and the presence of unilateral and bilateral visual acuity <0.7 was investigated using multiple logistic regression adjusted for important disturbance variables. RESULTS: Data from 189,704 children (91,041 girls, 98,663 boys) from 35 out of 36 districts were included. A visual acuity <0.7 was measured in 8416 (4.4%) children and in both eyes in 4345 (2.3%) children. The participation rates in the U8 and U9 were 93.9% and 93.3%, respectively. There was a negative association between participation in the U8 and U9 and a unilateral or bilateral SEU visual acuity <0.7 (adjusted odds ratio, OR 0.68, 95% confidence interval, CI 0.61-0.75; p < 0.01, N = 124,467/adjusted OR 0.57, 95% CI 0.51-0.65; p < 0.01, N = 121,496). CONCLUSION: The proportion of children with visual acuity <0.7 at the SEU was high. Children who were examined in the U8 and U9 had a better chance for a good visual acuity in the school entry examination.

No Benefit of a Pediatric Screening in Discovering Reduced Visual Acuity in Children: Experiences from a Cross-Sectional Study in Germany.

BACKGROUND: The newly introduced German pediatric screening examination at the end of the third year of life (U7a) incorporates visual function testing in particular; there is no ophthalmic screening during childhood in Germany. The purpose of this study is to investigate the relationship between participation in U7a and visual function at the preschool health examination (PHE) in the sixth year of life. METHODS: This study evaluated PHE data from school enrollment years 2009/2010 to 2014/2015 of Rhineland-Palatinate, Germany. Visual acuity (VA) at PHE was assessed with Rodenstock visual acuity test device (tumbling E) wearing glasses if present. The relationship between participation in U7a and VA <0.7 at PHE was calculated for reduced monocular and binocular VA using multiple logistic regression adjusted for potential confounders. RESULTS: Data from 189,704 children (91,041 girls) in 35 out of 36 districts were included. The first children to participate in U7a were enrolled in 2011/2012 school year. In total, 90,339 children (47.6%) had U7a before PHE, while 99,365 (52.4%) had not. VA <0.7 in at least one eye was measured at PHE in 8429 (4.4%) children, and in both eyes in 4345 (2.3%) children. Participation in U7a was not associated with VA <0.7 at PHE (odds ratio 0.99; 95% confidence interval: 0.94-1.04). CONCLUSIONS: The proportion of children with VA <0.7 at PHE was high. No beneficial effect of newly introduced German U7a pediatric screening examination was found for reduced VA at PHE.

Saccadic reaction time and ocular findings in phenylketonuria.

BACKGROUND: Phenylketonuria (PKU) is an inherited metabolic disorder characterized by reduced activity of phenylalanine hydroxylase resulting in elevated blood phenylalanine (Phe) concentration. Despite some obvious ocular changes, the disorder has been poorly recognized by ophthalmologists. Neurophysiologic tests imply prolonged reaction time correlating with increased phenylalanine blood concentrations. We aimed to test saccadic reaction time in PKU patients in dependency of blood phenylalanine concentrations. METHODS: Nineteen biochemically diagnosed PKU patients and 100 controls completed comprehensive ophthalmologic and orthoptic examinations including saccadometry by infrared based video-oculography. Peak velocity, gain, and particularly latency of reflexive saccades were compared to controls, and regression analysis was performed. RESULTS: Latency of reflexive saccades was not associated with the current phenylalanine concentration. Although in 10 out of 19 patients phenylalanine concentrations were outside the age-related therapeutic range, latency differed little between PKU patients and the controls, as well as peak velocity and gain. Ocular findings occurred as partial hypopigmentation of the iris in one late diagnosed patient aged 36 years, and as bilateral cataracts (possibly due to steroid intake) with refractive amblyopia, strabismus, high myopia, and glaucoma in another late diagnosed patient aged 46 years. Visual acuity was reduced in eight PKU patients. CONCLUSIONS: Saccadometry, particularly saccadic reaction time, is not useful in the monitoring of phenylketonuria. Ophthalmic examination is recommended in PKU patients, as the occurrence of ocular pathologies was relatively high.

[Orbital Inflammation: Current Trends]. / Orbitale Entzündung: aktuelle Trends.

The field of idiopathic orbital inflammation has come into motion: Ever since the first description of IgG4-associated disease about 10 years ago, the group of idiopathic lesions has shrunk by about half. The differential diagnosis has become much more demanding because the clinical and imaging overlap is considerable. This article presents a review of idiopathic orbital inflammation, IgG4-associated disease, and orbital lymphoid hyperplasia. All three conditions can have significant - and quite amazing - clinical and imaging similarities. At the same time, however, the necessity of diagnostic assessment differ just as much as the optimal therapy or therapy duration.

[Periocular Necrobiotic Xanthogranuloma with Mono- and Biclonal Gammopathy]. / Periokuläres nekrobiotisches Xanthogranulom bei mono- und biklonaler Gammopathie.

Necrobiotic xanthogranuloma is a very rare disease with granulomatous lesions of the skin with possible association with paraproteinemia. We report two cases of orbital necrobiotic xanthogranuloma in patients with mono/biclonal gammopathy of undetermined significance. Both patients underwent successful conservative treatment.

The Diagnosis and Treatment of Idiopathic Facial Paresis (Bell's Palsy).

BACKGROUND: Peripheral facial nerve palsy is the most com- mon functional disturbance of a cranial nerve. 60-75% of cases are idiopathic. METHODS: This review is based on a selective literature search proceeding from the current, updated German-language guideline on the diagnosis and treatment of idiopathic facial nerve palsy. RESULTS: The recommended drug treatment consists of prednisolone 25 mg bid for 10 days, or 60 mg qd for 5 days followed by a taper to off in decrements of 10 mg per day. This promotes full recovery (number needed to treat [NNT] = 10; 95% confidence interval [6; 20]) and lessens the risk of late sequelae such as synkinesia, autonomic disturbances, and contractures. Virostatic drugs are optional in severe cases (intense pain or suspicion of herpes zoster sine herpete) and mandatory in cases of varicella-zoster virus (VZV) infection. Corneal protection with dexpanthenol ophthalmic ointment, artificial tears, and a nocturnal moisture- retaining eye shield has been found useful in practice. In cases of incomplete recovery with residual facial weakness, both static and microsurgical dynamic methods can be used to restore facial nerve function. CONCLUSION: Because 25-40% of cases of facial nerve palsy are not idiopathic, differential diagnosis is very important; key diagnostic methods include a clinical neurological examin- ation, otoscopy, and a lumbar puncture for cerebrospinal fluid examination. High-level evidence supports corticosteroid treatment for the idiopathic form of the disorder.

A comprehensive monocentric ophthalmic study with Gaucher disease type 3 patients: vitreoretinal lesions, retinal atrophy and characterization of abnormal saccades.

BACKGROUND: The differentiation between Gaucher disease type 3 (GD3) and type 1 is challenging because pathognomonic neurologic symptoms may be subtle and develop at late stages. The ophthalmologist plays a crucial role in identifying the typical impairment of horizontal saccadic eye movements, followed by vertical ones. Little is known about further ocular involvement. The aim of this monocentric cohort study is to comprehensively describe the ophthalmological features of Gaucher disease type 3. We suggest recommendations for a set of useful ophthalmologic investigations for diagnosis and follow up and for saccadometry parameters enabling a correlation to disease severity. METHODS: Sixteen patients with biochemically and genetically diagnosed GD3 completed ophthalmologic examination including optical coherence tomography (OCT), clinical oculomotor assessment and saccadometry by infrared based video-oculography. Saccadic peak velocity, gain and latency were compared to 100 healthy controls, using parametric tests. Correlations between saccadic assessment and clinical parameters were calculated. RESULTS: Peripapillary subretinal drusen-like deposits with retinal atrophy (2/16), preretinal opacities of the vitreous (4/16) and increased retinal vessel tortuosity (3/16) were found. Oculomotor pathology with clinically slowed saccades was more frequent horizontally (15/16) than vertically (12/16). Saccadometry revealed slowed peak velocity compared to 100 controls (most evident horizontally and downwards). Saccades were delayed and hypometric. Best correlating with SARA (scale for the assessment and rating of ataxia), disease duration, mSST (modified Severity Scoring Tool) and reduced IQ was peak velocity (both up- and downwards). Motility restriction occurred in 8/16 patients affecting horizontal eye movements, while vertical motility restriction was seen less frequently. Impaired abduction presented with esophoria or esotropia, the latter in combination with reduced stereopsis. CONCLUSIONS: Vitreoretinal lesions may occur in 25% of Gaucher type 3 patients, while we additionally observed subretinal lesions with retinal atrophy in advanced disease stages. Vertical saccadic peak velocity seems the most promising "biomarker" for neuropathic manifestation for future longitudinal studies, as it correlates best with other neurologic symptoms. Apart from the well documented abduction deficit in Gaucher type 3 we were able to demonstrate motility impairment in all directions of gaze.

Intact Visuospatial Cognition in Amblyopia: Results From the Gutenberg Health Study.

PURPOSE: To determine whether amblyopia interferes with cognitive functions requiring visuospatial processing, measured by the Tower of London (ToL) test. METHODS: The current study was based on a sub-cohort from the population-based Gutenberg Health Study and included 1,569 participants aged 35 to 44 years. Amblyopia was defined as a visual acuity of 0.63 or worse (worse eye) in the presence of an amblyogenic factor; prevalence was 5%. There were three groups: participants with amblyopia (n = 78), participants with a visual acuity of 0.63 or worse (worse eye) without amblyopia (n = 65), and participants with a visual acuity of better than 0.63 (worse eye) (n = 1,426). Visuospatial planning ability was measured by the ToL test (touch-screen version), and the performance score ranged from 0 to 24, depending on the number of correctly solved problems. The authors used linear regression models to investigate the association between amblyopia and ToL test scores, adjusting for age, sex, and socioeconomic status. RESULTS: The mean ± standard deviation of ToL test performance was 15.31 ± 3.29 in participants with a visual acuity of better than 0.63, 14.56 ± 3.76 in the amblyopic group, and 15.14 ± 3.65 in participants with a visual acuity of 0.63 or worse without amblyopia. In a linear regression model, sex, and socioeconomic status significantly predicted planning performance (P <.0001), whereas amblyopic status did not (P = .20). CONCLUSIONS: Amblyopia may affect visuospatial perception, but no such relationships could be found for higher cognitive functions that strongly depend on visuospatial processing. Thus, in adulthood, individuals with amblyopia are unaffected in their visuospatial cognitive abilities, as required by the ToL test. [J Pediatr Ophthalmol Strabismus. 2019;56(6):397-401.].

Ophthalmological Findings in Mucopolysaccharidoses.

The mucopolysaccharidoses (MPS) are a heterogenous group of lysosomal storage disorders caused by the accumulation of glycosaminoglycans (GAGs). The accrual of these compounds results in phenotypically varied syndromes that produce multi-organ impairment with widespread systemic effects. The low incidence of MPS (approximately 1/25,000 live births) in conjunction with the high childhood mortality rate had limited the availability of research into certain clinical features, especially ocular manifestations. As the recent successes of hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) have greatly increased life expectancy in these patients, they have served as a focal point for the transition of research towards improvement of quality of life. Ophthalmological findings in MPS include corneal clouding, glaucoma, optic neuropathies, and retinopathies. While corneal clouding is the most common ocular feature of MPS (especially type I, IVA, and VI), its response to HSCT and ERT is minimal. This review discusses known eye issues in the MPS subtypes, diagnosis of these ocular diseases, current clinical and surgical management, noteworthy research progress, and ultimately presents a direction for future studies.

Ocular ductions after rectus muscle recession and resection in thyroid eye disease.

Background: Recession and resection of rectus muscles for correction of strabismus in Thyroid Eye Disease (TED) is relatively unpopular as it is assumed to enhance the restriction of ocular ductions. Therefore, the purpose of this study was to compare ductions of recession only and recess/resect procedures. Methods: We retrospectively reviewed the charts of 119 patients who underwent strabismus surgery for TED from 1991 to 2015, of which 102 were included in the present study. Forty-six interventions were performed on horizontal, 56 on vertical rectus muscles; comprising 41 recess/resect surgeries for horizontal deviations, and 7 in patients with vertical strabismus. Ocular ductions and alignment were evaluated preoperatively and at 3 and 12 months postoperatively. Results: Both recessions as well as recess/resect procedures resulted in improved abduction and elevation, respectively. At the exam 3 months postoperatively, median abduction for the recession only group and the recess/resect group were 27.5° and 35°, respectively. The similar figures for elevation were 25° and 10°, respectively. Neither were statistically significant. No restricted adduction or depression was seen in the recess/resect surgeries groups with lateral or superior rectus resection. None of the patients showed unusual postoperative inflammation or conjunctival scarring. Conclusion: In this retrospective analysis, we found an equal effect on ocular ductions in patients with TED when comparing recess/resect eye muscle surgery to recess only procedures. In TED patients with large horizontal angle deviations and abduction deficit, medial rectus recession and lateral rectus resection surgery can be considered. Muscle resections in TED do not seem to have a clinically relevant risk to increase the restriction of ocular ductions but rather improve ductions in the restricted directions of gaze.

Corneal topometric, aberrometric and biomechanical parameters in mucopolysaccharidosis patients.

AIMS: To report corneal topometric and aberrometric values in mucopolysaccharidosis (MPS) and to investigate their correlation with biomechanical corneal parameters. METHODS: One randomly chosen eye of 20 MPS patients with no to moderate corneal clouding and one eye of 23 healthy controls with comparable age were prospectively included into this study. Corneal surface regularity was assessed by index of surface variance (ISV), -vertical asymmetry (IVA), -height asymmetry (IHA), -height decentration (IHD); keratoconus index (KI), central keratoconus index (CKI) and Zernike indices of anterior and posterior corneal surface using Scheimpflug imaging (Pentacam). Corneal resistance factor (CRF) and corneal hysteresis (CH) were assessed by Ocular Response Analyzer. Statistical analyses were performed using Mann-Whitney-Test and Spearman Correlation Coefficients. RESULTS: IVA, ISV, IHD, IHA, but not KI and CKI were significantly higher in MPS patients compared to age matched healthy controls. Spherical aberration and asphericity coefficients either at the anterior or at the posterior corneal surface differed significantly between both groups. The grade of the MPS-associated corneal opacity correlated significantly with ISV (rho = 0.52), IVA (rho = 0.54), IHA (rho = 0.57) and IHD (rho = 0.48). Density of the MPS-affected corneas correlated significantly with ISV (rho = 0.52), IVA (rho = 0.72), IHA (rho = 0.57), IHD (rho = 0.69), 3rd order horizontal trefoil aberration at the posterior (rho = 0.62) and anterior surface (rho = 0.48) as well as with CH (rho = 0.55) and CRF (rho = 0.57). Spherical aberration at the back surface correlated with CRF and CH in MPS and in healthy controls. CONCLUSIONS: This is the first study analyzing shape of the corneal surface in MPS patients. Topometric indices of corneal asymmetry are significantly increased and correlate with MPS-related corneal opacity and density. Spherical aberration and asphericity coefficient at the front and at the back corneal surface differ significantly between MPS and healthy controls.