Three-Dimensional Quantitative Magnetic Resonance Imaging Cartilage Evaluation of the Hand Joints of Systemic Sclerosis Patients: A Novel Insight on Hand Osteoarthritis Pathogenesis-Preliminary Report.

BACKGROUND: Osteoarthritis of the hand joints in systemic sclerosis (SSc) patients might be an independent manifestation leading to limitation of upper extremity function. There is no publication quantitatively assessing the thickness of articular cartilage within the hand joints of SSc patients by MRI. The purpose of our study was to quantify the condition and thickness of hand joints cartilage with three-dimensional quantitative MRI (3D q-MRI). METHODS: The study was conducted in twenty people: ten patients with SSc and ten healthy individuals. All participants were examined with the 3D q-MRI with 3T scanner. The cartilage thickness of proximal (PIP) and distal interphalangeal (DIP) joints as well as metacarpophalangeal joints was measured. RESULTS: There was no significant difference in cartilage thickness between both groups. However, the joint cartilage was thinner in fingers with acro-osteolysis. In PIP joint of the fingers with acro-osteolysis, the mean cartilage thickness was 0.5 mm (p = 0.0043) and 0.4 mm (p = 0.0034) in DIP joints. CONCLUSIONS: Quantitative MRI analysis of the joints of the hands of SSc patients does not indicate changes in thickness of the articular cartilage. A significant reduction in the articular cartilage thickness of the fingers with acro-osteolysis indicates the potential of an ischemic basis of articular cartilage destruction in SSc patients.

Searching for Effective Methods of Diagnosing Nervous System Lesions in Patients with Alström and Bardet-Biedl Syndromes.

Bardet-Biedl syndrome (BBS) and Alström syndrome (ALMS) are rare multisystem diseases with an autosomal recessive mode of inheritance and genetic heterogeneity, characterized by visual impairment, hearing impairment, cardiomyopathy, childhood obesity, and insulin resistance. The purpose of our study was to evaluate the indicators of nervous system changes occurring in patients with ALMS and BBS using optical coherence tomography (OCT) and magnetic resonance spectroscopy (MRS) methods compared to a group of healthy subjects. The OCT results showed significantly lower macular thickness in the patient group compared to the control group (p = 0.002). The MRS study observed differences in metabolite levels between the study and control groups in brain areas such as the cerebellum, thalamus, and white matter. After summing the concentrations from all areas, statistically significant results were obtained for N-acetylaspartate, total N-acetylaspartate, and total creatine. Concentrations of these metabolites were reduced in ALMS/BBS patients by 38% (p = 0.0004), 35% (p = 0.0008), and 28% (p = 0.0005), respectively. Our results may help to understand the pathophysiology of these rare diseases and identify strategies for new therapies.

Reduced Corneal Sensitivity With Neuronal Degeneration is a Novel Clinical Feature in Wolfram Syndrome.

PURPOSE: To evaluate corneal sensitivity and corneal nerve morphology among patients with Wolfram syndrome (WFS). DESIGN: An observational clinical case series with confirmatory experiments. METHODS: We included a group of 12 patients with biallelic mutations in the WFS1 gene and a control group composed of 30 individuals with type 1 diabetes (T1D). All participants (n = 42) underwent a complete ophthalmic examination, esthesiometry, and retinal nerve fiber layer assessment using optical coherence tomography. Morphologic assessment of corneal neuropathy by in vivo corneal confocal microscopy was conducted in 11 patients with WFS (both eyes) and 1 WFS patient (1 eye) as well as in 24 patients with T1D (both eyes in 6 patients and 1 eye in 18 patients). Additionally, corneas from Wfs1KO mice and their wild-type littermates were subjected to laser scanning confocal microscopy. RESULTS: Corneal sensitivity was significantly reduced in patients with WFS compared with patients with T1D (4.50 cm [interquartile range, 3.50-5.50 cm] vs 6.00 cm [interquartile range, 6.00-6.00 cm]; P < 10-5). Additionally, corneal nerve fiber and branch density as well as nerve fiber length were low among patients with WFS. Corneal sensitivity correlated with macular average thickness (R = 0.6928; P = .039) and best-corrected visual acuity (R = -0.61; P = .002) in the WFS group. Similarly, Wfs1 knockout mice also presented corneal neurodegeneration changes when corneal nerve fiber density and length were measured using laser scanning confocal microscopy. CONCLUSIONS: Decreased corneal sensitivity and corneal nerve degeneration are observed in WFS. Corneal sensitivity is linked with the degree of disease progression as measured by visual acuity and retinal thinning.

Role and effectiveness of complex and supervised rehabilitation on overall and hand function in systemic sclerosis patients-one-year follow-up study.

The aim of this study was to estimate the long-term results of complex and supervised rehabilitation of the hands in systemic sclerosis (SSc) patients. Fifty-one patients were enrolled in this study: 27 patients (study group) were treated with a 4-week complex, supervised rehabilitation protocol. The control group of 24 patients was prescribed a home exercise program alone. Both groups were evaluated at baseline and after 1-, 3-, 6-, and 12-months of follow-up with the Disability of the Arm, Shoulder and Hand Questionnaire (DAHS) as the primary outcome, pain (VAS-visual analog scale), Cochin Hand Function Scale (CHFS), Health Assessment Questionnaire Disability Index (HAQ-DI), Scleroderma-HAQ (SHAQ), range of motion (d-FTP-delta finger to palm, Kapandji finger opposition test) and hand grip and pinch as the secondary outcomes. Only the study group showed significant improvements in the DASH, VAS, CHFS and SHAQ after 1, 3 and 6 months of follow-up (P = 0.0001). Additionally, moderate correlations between the DASH, CHFS and SHAQ (R = 0.7203; R = 0.6788; P = 0.0001) were found. Complex, supervised rehabilitation improves hand and overall function in SSc patients up to 6 months after the treatment but not in the long term. The regular repetition of this rehabilitation program should be recommended every 3-6 months to maintain better hand and overall function.

Clinical Application and Efficacy of Silver Drug in Ophthalmology: A Literature Review and New Formulation of EYE Drops with Drug Silver (I) Complex of Metronidazole with Improved Dosage Form.

The use of silver preparations in medicine is becoming increasingly popular. The basic aim of this evaluation was to review the literature on the clinical (in vivo) and antibacterial potential of silver preparations in ophthalmic diseases. The second goal was to summarize the results of experimental research on the use of silver preparations in ophthalmology. The third objective was to present a method for stabilizing eye drops containing silver (I) complex. Analysis of the pH stability of the silver (I) complex with metronidazole in the prepared dosage form (eye drops) was carried out. Most silver preparations are clinically used for topical application. Few experimental results indicate the usefulness of intraocular or systemic administration of silver (I) preparations as an alternative or additional therapy in infectious and angiogenic eye diseases. The development of a new formulation increases the stability of the dosage form. New forms of silver (I) products will certainly find application in the treatment of many ophthalmic diseases. One of the most important features of the silver (I) complex is its capacity to break down bacterial resistance. The new eye drops formula can significantly improve comfort of use. Due to their chemical nature, silver (I) compounds are difficult to stabilize, especially in the finished dosage form.

Serum microRNA as indicators of Wolfram syndrome's progression in neuroimaging studies.

INTRODUCTION: Patients with the ultra-rare Wolfram syndrome (WFS) develop insulin-dependent diabetes and progressive neurodegeneration. The aim of the study was to quantify microRNAs (miRNAs) in sera from patients with WFS, correlate their expression with neurological imaging over time and compare miRNA levels with those observed in patients with type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS: We quantified miRNA expression (Qiagen, Germany) in two groups of patients: with WFS at study entry (n=14) and after 2 years of follow-up and in 15 glycated hemoglobin-matched (p=0.72) patients with T1DM. RESULTS: We observed dynamic changes in the expression of multiple miRNAs in patients with WFS parallel to disease progression and in comparison to the T1DM patients group. Among miRNAs that differed between baseline and follow-up WFS samples, the level of 5 increased over time (miR-375, miR-30d-5p, miR-30e-30, miR-145-5p and miR-193a-5p) and was inversely correlated with macular average thickness, while the expression of 2 (let-7g-5p and miR-22-3p) decreased and was directly correlated with neuroimaging indicators of neurodegeneration. CONCLUSIONS: Our findings show for the first time that serum miRNAs can be used as easily accessible indicators of disease progression in patients with WFS, potentially facilitating clinical trials on mitigating neurodegeneration.

Matrix Metalloproteinases MMP-2 and MMP-9, Their Inhibitors TIMP-1 and TIMP-2, Vascular Endothelial Growth Factor and sVEGFR-2 as Predictive Markers of Ischemic Retinopathy in Patients with Systemic Sclerosis-Case Series Report.

Systemic sclerosis (SSc) is an autoimmune connective tissue disorder associated with multiple organ involvement. The aim of the study was to present two SSc patients who were diagnosed with ischemic retinopathy in both eyes. As a background to our case study, we decided to investigate the imbalance of angiogenesis factors in 25 SSc patients in relation to 25 healthy controls. Assays of matrix metalloproteinases-2 and -9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1) and -2 (TIMP-2), vascular endothelial growth factor (VEGF), and soluble VEGF receptor-2 (sVEGFR-2) in blood serum and tears were performed. A significantly increased levels of MMP-9 in serum and tears, (p = 0.0375 and p < 0.001, respectively) as well as VEGF/sVEGFR-2 ratio in tears (p < 0.001) were found in the whole SSc patients group compared with controls, while reduced levels of these parameters in patients with ischemic sclerodermic retinopathy were noted. We also observed decreased level MMP-2 in tears and increased levels of TIMP-2 in blood serum and tears of SSc patients with retinal ischemic changes. MMP-9, MMP-2, TIMP-2, and VEGF/sVEGFR-2 may play a crucial role in ischemic retinal degeneration or retinal reorganization in SSc.

Conjunctival Ultraviolet Autofluorescence as a Measure of Riboflavin and Ultraviolet and Accelerated Cross-Linking Exposure in Keratoconic Patients.

PURPOSE: The study was performed to analyze the prevalence of the conjunctival ultraviolet autofluorescence (CUVAF) area in keratoconic eyes and changes caused by UVA-irradiation as a component of accelerated corneal cross-linking (aCXL). METHODS: The study group involved 20 keratoconic patients subjected to aCXL surgery in one eye. The comparative group consisted of 111 age- and sex-matched patients with healthy corneas. The images of the anterior segment in both patient groups were taken using a Coroneo camera. In the study group the photos were taken before and immediately after the surgery, and 7 and 30 days following the procedure. RESULTS: Nasal and temporal autofluorescence area (AN+T) were significantly smaller in a keratoconic patients group compared to control group (p = 0.0001). Patients with the third stage of keratoconus had significantly higher AN+T (p = 0.0277) compared with individuals with lower stage keratoconus. No statistically significant CUVAF changes were observed after the aCXL procedure. In keratoconic patients with primary CUVAF undergoing aCXL, a temporary fast enlargement of the autofluorescence area was observed. CONCLUSIONS: The eyes undergoing the aCXL procedure showed no difference in the size of the CUVAF area but such patients should be in strict follow-up in order to reveal UV-related ocular surface diseases.

Multiple Retinal Anomalies in Wfs1-Deficient Mice.

BACKGROUND: Wolfram syndrome (WFS, OMIM: #222300) is an ultrarare autosomal recessive disorder characterized by diabetes insipidus, diabetes mellitus, optic nerve atrophy and deafness. It has been reported that the average retinal thickness in WFS patients decreases with the progression of the disease. AIM: To investigate retinal thickness and wolframin expression disorders in Wolfram syndrome 1 gene knockout (Wfs1KO) mice compared to their wild-type (WT) littermates. MATERIALS AND METHODS: Both bulbs with optic nerves of three mice Wfs1WT and three Wfs1KO were taken for the histopathological examination. A strain of knockout mice with mutation in exon 8 was used. RESULTS: No expression of wolframin protein in the retina and neurodegeneration of the optic nerve of Wfs1KO mice as compared among Wfs1WT mice was observed. The mean central retinal thickness was thinner and the retinal thickness/longitudinal diameter ratio was significantly lower in hte Wfs1KO as compared to the Wfs1WT mice. In four (67%) eyeballs of Wfs1KO mice, intra-retinal neovessels were observed. CONCLUSIONS: Wfs1KO mice retina with mutation in exon 8 present similar clinical features as patients with WFS in the form of reduced retinal thickness and neurodegeneration of the optic nerve. The presence of proliferative retinopathy observed in Wfs1KO mice requires further investigation.

Effect of treatment with silver(I) complex of metronidazole on ocular rosacea: Design and formulation of new silver drug with potent antimicrobial activity.

BACKGROUND: Metronidazole with well-soluble silver nitrate forms a complex with potent activity (synergism) against bacterial strains and fungi with simultaneous lower side effect than in the case of the two agents administered separately. This study aimed to establish effectiveness in the treatment of ocular rosacea with new formulation of drops and ointment with silver(I) complex of metronidazole. METHODS: Three patients suffering from serious ophthalmic complications of acne rosacea were treated with drops and ointments applied 3 times a day for 3 months. The uncorrected visual acuity testing (UCVA), pachymetry as well as subjective and objective tear film assessment were evaluated. RESULTS: In all patients, we have improved UCVA as well as objective and subjective evaluation of the tear film parameters. No significant differences in corneal thickness were observed. CONCLUSION: Well soluble silver(I) complex of metronidazole might be an alternative method in ophthalmic complications of acne rosacea treatment.

The Role of Angiogenesis Factors in the Formation of Vascular Changes in Scleroderma by Assessment of the Concentrations of VEGF and sVEGFR2 in Blood Serum and Tear Fluid.

Systemic sclerosis (SSc) is a connective tissue disorder characterized by tissue hypoxia, excessive fibrosis of skin and internal organs, and angiogenesis imbalance. The aim of the study was to evaluate in SSc patients the association between the retinal microcirculation disturbances and the presence of peripheral trophic changes and to determine the role of angiogenesis factors in the formation of vascular changes in scleroderma. Twenty-five SSc patients and 25 age- and sex-matched healthy controls were included to the study. Assay of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-2 (sVEGFR-2) in blood serum and tears was done for all patients and controls using enzyme-linked immunosorbent assay. Retinal blood circulation was investigated with fluorescein angiography (FA) in the SSc patients only. In our research, proportion of mainly hypertensive patients presenting with a large spectrum of retinal microvascular lesions was 72%, while proportion of patients with skin microvascular lesions within distal phalanxes of fingers and toes was 76%. We noticed that patients with pathological changes in the FA examination had finger ulcerations significantly more often than patients without changes in the eye fundus. There were no statistically significant differences in the serum concentration of VEGF and sVEGFR2 between subjects in both analyzed groups. Analysis of lower levels of VEGF (p = <0.001) and sVEGFR-2 (p = <0.001) in blood serum accompanied by simultaneous higher levels of VEGF/sVEGFR-2 ratio in tears of SSc patients, as compared with the control group, indicates the superiority of proangiogenic factors in patients' tears.

Corneal Abnormalities Are Novel Clinical Feature in Wolfram Syndrome.

PURPOSE: To evaluate corneal morphology among patients with Wolfram syndrome (WFS). DESIGN: Comparative observational longitudinal case series of WFS patients with a laboratory approach in the WFS1 gene knockout (Wfs1KO) mouse model. METHODS: A group of 12 patients with biallelic mutations in the WFS1 gene recruited from the whole country and a control group composed of 30 individuals with type 1 diabetes (T1D) were evaluated in a national reference center for monogenic diabetes. All subjects (n = 42) underwent a complete ophthalmic examination, computer videokeratography, and corneal thickness and endothelial measurements. Additionally, WFS patients (n = 9) underwent longitudinal videokeratography and Pentacam evaluation. Corneal characteristics were assessed and compared between both groups. Human and mouse corneas were subjected to immunohistochemistry to detect wolframin expression and microscopic evaluation to study corneal morphology ex vivo. RESULTS: Clinical and topographic abnormalities similar to keratoconus were observed in 14 eyes (58.3%) of 8 WFS patients (66.7%). Flat keratometry, inferior-superior dioptric asymmetry, skewed radial axis, logarithm of keratoconus percentage index, index of surface variance, index of vertical asymmetry, keratoconus index, central keratoconus index, index of height asymmetry, and index of height decentration differed between WFS and T1D patients. Immunohistochemistry demonstrated wolframin expression in human and mouse corneas. Compared with Wfs1WT mice, Wfs1KO mice also presented corneal abnormalities. CONCLUSIONS: Patients with WFS present a high prevalence of changes in corneal morphology compatible with the diagnosis of early stages of keratoconus. Observations in a mouse model suggest that a mutation in the WFS1 gene may be responsible for corneal abnormalities similar to keratoconus.

Can we effectively predict the occurrence of cerebral edema in children with ketoacidosis in the course of type 1 diabetes? - case report and literature review.

Background Cerebral edema (CE) is one of the most serious complications of diabetic ketoacidosis (DKA) and can result in central nervous system (CNS) disorders and even lead to death of the patient. Case presentation We present the case of a 11-year-old boy with severe DKA in the course of newly diagnosed type 1 diabetes (T1D). The delay in the diagnosis of DKA and some therapeutic problems contributed to the development of CE and direct life-threatening conditions. Early diagnosis of CE development in the course of DKA using non-invasive methods such as pachymetry or transorbital ultrasound seems to be a very important prognostic factor. Conclusions This case highlights the importance of appropriate treatment according to the newest recommendations and presents the usefulness of new diagnostic methods to assess the risk of CE in children with newly diagnosed T1D.

Central Corneal Thickness can be Related to Diabetic Peripheral Neuropathy in Children with Type 1 Diabetes.

AIMS: Diabetic eye disease with its various manifestations as well as diabetic neuropathy may occur in patients with type 1 diabetes (T1D) after several years of diabetes duration. Pachymetry is a promising method evaluating central corneal thickness (CCT) in diabetic patients. The aim of the study was to evaluate the CCT values in children with T1D and its relationship to neurophysiological markers of diabetic neuropathy. METHODS: The study groups included 119 T1D children with average 5.3 years of diabetes duration and 38 age-matched controls. CCT index was measured with pachymeter in all subjects and in 19/119 of T1D patients the CCT values were referred to the ENG-EMG-SSR study results. RESULTS: In T1D patients the higher CCT values were observed as compared to healthy controls (p=0.037). Correlations between CCT values and both distal latency of the motor fibers of the median nerve (R=0.51; p=0.044) and conduction velocity of this nerve (R=-0.55; p=0.027) were noted. A conduction velocity of the sensory fibers of sural nerve correlated negatively with CCT index (R=-0.50; p=0.045) in the T1D patients. CONCLUSIONS: CCT measurement may be helpful in the referral of the asymptomatic pediatric T1D patients to assess an early stage of diabetic neuropathy.

The HD-OCT Study May Be Useful in Searching for Markers of Preclinical Stage of Diabetic Retinopathy in Patients with Type 1 Diabetes.

The aim of the study was to analyze the thickness of individual retinal layers in patients with type 1 diabetes (T1D) in comparison to the control group and in relation to markers of diabetes metabolic control. The study group consisted of 111 patients with an average of 6-years of T1D duration. The control group included 36 gender- and age-matched individuals. In all patients optical coherence tomography (OCT) study was performed using HD-OCT Cirrus 5000 with evaluation of optic nerve head (ONH) parameters, thickness of retinal nerve fiber layer (RNFL) with its quadrants, macular full-thickness parameters, ganglion cells with inner plexus layer (GCIPL) and choroidal thickness (CT). Lower disc area value was observed in the study group as compared to controls (p = 0.0215). Negative correlations were found both between age at examination and rim area (R = -0.28, p = 0.0007) and between superior RNFL thickness and duration of diabetes (R = -0.20, p = 0.0336). Positive correlation between center thickness and SD for average glycemia (R = 0.30, p = 0.0071) was noted. Temporal CT correlated positively with age at examination (R = 0.21, p = 0.0127). The selected parameters the HD-OCT study may in the future serve as potential markers of preclinical phase of DR in patients with T1D.

Optical coherence tomography and magnetic resonance imaging visual pathway evaluation in Wolfram syndrome.

AIM: The aim of this study was to assess parameters of retinal morphology by using high-definition optical coherence tomography (OCT) in patients with Wolfram syndrome (WFS) and their relation to optic tract atrophy in magnetic resonance imaging (MRI). METHOD: High-definition OCT and MRI parameters were evaluated in 12 patients with WFS (three males, nine females; median age at examination 12y 8mo, range 10y 2mo-15y 11mo) and referred to 30 individuals with type 1 diabetes (T1D) (12 males, 18 females; median age at examination 20y 5mo, range 16y 8mo-21y 4mo) and 33 typically developing comparison participants (10 males, 23 females; median age at examination 20y 7mo, range 13y-22y 4mo). RESULTS: Total thickness and quadrant thickness of the retinal nerve fibre layer (RNFL), macular full-thickness parameters and macular ganglion cell layer/inner plexiform layer, intraorbital and intracranial thickness of the optical nerve, as well as the optic chiasm and visual tracts were significantly reduced in patients with WFS compared with those having T1D and the typically developing comparison participants. Optic chiasm thickness correlated negatively in patients with WFS with both age (r=-0.79; p=0.002) and duration of diabetes (r=-0.62; p=0.032). Thickness of the intraorbital parts of the optic nerves in patients with WFS correlated positively with thickness of the superior RNFL (r=0.73; p=0.006). INTERPRETATION: High-definition OCT in combination with MRI could become an important tool for evaluating the effectiveness of therapeutic trials in patients with WFS. WHAT THIS PAPER ADDS: Provides evidence of significant reduction of retinal parameters and optic nerves in patients with Wolfram syndrome (WFS). Shows correlations between magnetic resonance imaging parameters and retinal morphology parameters in patients with WFS.

Measurement of corneal thickness, optic nerve sheath diameter and retinal nerve fiber layer as potential new non-invasive methods in assessing a risk of cerebral edema in type 1 diabetes in children.

AIMS: Some patients with diabetic ketoacidosis develop cerebral edema (CE) in the course of type 1 diabetes mellitus (T1D), which may result in central nervous system disorders and high mortality. The imperfection of existing neuroimaging techniques for early recognition of CE forces us to search for the new and non-invasive methods. The aim of the study was to assess the usefulness of new methods (pachymetry, transorbital ultrasonography-USG, optical coherence tomography-OCT study) in the assessment of the risk of CE occurrence in children with newly diagnosed T1D. METHODS: The study group included 50 children with newly diagnosed T1D, 54 patients with long-term T1D as a reference group and 40 children without glucose tolerance disorders as controls. In all subjects, a corneal thickness (CCT) index with pachymeter, optic nerve sheath diameter (ONSD) using transorbital USG and retinal nerve fiber layer (RNFL) during OCT study were measured and compared with selected clinical parameters of T1D. RESULTS: In patients from a study group at onset of T1D, the higher CCT (p < 0.001) and ONSD (p < 0.001) values were observed as compared to the results obtained after 48 h of metabolic compensation. The ONSD correlated negatively with pH value (r = - 0.64; p < 0.001), BE (r = - 0.54, p < 0.001) and HCO3- (r = - 0.50; p < 0.001). A positive correlation between RNFL and Na+ levels (r = 0.47; p < 0.005) was also observed. CONCLUSIONS: Transorbital USG and pachymetry may serve as the potential promising methods for the non-invasive assessment of the increased risk of development of CE in patients with T1D.

Serum Metabolic Fingerprinting Identified Putatively Annotated Sphinganine Isomer as a Biomarker of Wolfram Syndrome.

Wolfram syndrome (WFS) is an example of a rare neurodegenerative disease with coexisting endocrine symptoms including diabetes mellitus as the first clinical symptom. Treatment of WFS is still only symptomatic and associated with poor prognosis. Potential markers of disease progression that could be useful for possible intervention trials are not available. Metabolomics has potential to identify such markers. In the present study, serum fingerprinting by LC-QTOF-MS was performed in patients with WFS (n = 13) and in patients with T1D (n = 27). On the basis of the obtained results, aminoheptadecanediol (17:0 sphinganine isomer) (+50%, p = 0.02), as the most discriminatory metabolite, was selected for validation. The 17:0 sphinganine isomer level was determined using the LC-QQQ method in the samples from WFS patients at two time points and compared with samples obtained from patients with T1D (n = 24) and healthy controls (n = 24). Validation analysis showed higher 17:0 sphinganine isomer level in patients with WFS compared to patients with T1D (p = 0.0097) and control group (p < 0.0001) with progressive reduction of its level after two-year follow-up period. Patients with WFS show a unique serum metabolic fingerprint, differentiating them from patients with T1D. Sphinganine derivate seems to be a marker of the ongoing process of neurodegeneration in WFS patients.

Retinal thickness as a marker of disease progression in longitudinal observation of patients with Wolfram syndrome.

AIMS: Wolfram syndrome (WFS) is a recessively inherited monogenic form of diabetes coexisting with optic atrophy and neurodegenerative disorders with no currently recognized markers of disease progression. The aim of the study was to evaluate retinal parameters by using optical coherence tomography (OCT) in WFS patients after 2 years of follow-up and analysis of the parameters in relation to visual acuity. METHODS: OCT parameters and visual acuity were measured in 12 WFS patients and 31 individuals with type 1 diabetes. RESULTS: Total thickness of the retinal nerve fiber layer (RNFL), average retinal thickness and total retinal volume decreased in comparison with previous OCT examination. Significant decreases were noted for RNFL (average difference -17.92 µm 95% CI -30.74 to -0.10; p = 0.0157), macular average thickness (average difference -5.38 µm 95% CI -10.63 to -2.36; p = 0.0067) and total retinal volume (average difference -0.15 mm3 95% CI -0.30 to -0.07; p = 0.0070). Central thickness remained unchanged (average difference 1.5 µm 95% CI -7.61 to 10.61; p = 0.71). Visual acuity of WFS patients showed a strong negative correlation with diabetes duration (R = -0.82; p = 0.0010). After division of WFS patients into two groups (with low-vision and blind patients), all OCT parameters except for the RNFL value were lower in blind WFS patients. CONCLUSIONS: OCT measures structural parameters and can precede visual acuity loss. The OCT study in WFS patients should be performed longitudinally, and serial retinal examinations may be helpful as a potential end point for future clinical trials.