Obesity, body fat distribution and eye diseases.

BACKGROUND: The prevalence of obesity, a chronic disease, is increasing, and obesity is now considered a global epidemic. Eye diseases are also increasing worldwide and have serious repercussions on quality of life as well as increasingly high costs for the community. The relationships between obesity and ocular pathologies are not yet well clarified and are not pathologically homogeneous: they seem to be somehow linked to excess body fat, especially to the distribution of adipose tissue and its ectopic deposits. PURPOSE: Our objective was to examine the associations between obesity and anthropometric indices, including body mass index (BMI), waist circumference (WC), and the waist/hip ratio (WHR), and the risk of most widespread eye diseases, with particular attention given to the most significant metabolic mechanisms. METHODS: This article provides a narrative overview of the effect of obesity and anthropometric measurements of body fat on prevalent eye diseases. We used the MEDLINE/PubMed, CINAHL, EMBASE, and Cochrane Library databases from 1984 to 2024. In addition, we hand-searched references from the retrieved articles and explored a number of related websites. A total of 153 publications were considered. RESULTS: There is significant evidence that obesity is associated with several eye diseases. Waist circumference (WC) and the waist/hip ratio (WHR) have been observed to have stronger positive associations with eye diseases than BMI. CONCLUSIONS: Obesity must be considered a significant risk factor for eye diseases; hence, a multidisciplinary and multidimensional approach to treating obesity, which also affects ocular health, is important. In the prevention and treatment of eye diseases related to obesity, lifestyle factors, especially diet and physical activity, as well as weight changes, both weight loss and weight gain, should not be overlooked. LEVEL OF EVIDENCE: Level V narrative review.

CSF levels of Chitinase3like1 correlate with early response to cladribine in multiple sclerosis.

Background: Cladribine has been introduced as a high-efficacy drug for treating relapsing-remitting multiple sclerosis (RRMS). Initial cohort studies showed early disease activity in the first year after drug initiation. Biomarkers that can predict early disease activity are needed. Aim: To estimate cerebrospinal fluid (CSF) markers of clinical and radiological responses after initiation of cladribine. Methods: Forty-two RRMS patients (30F/12M) treated with cladribine were included in a longitudinal prospective study. All patients underwent a CSF examination at treatment initiation, clinical follow-up including Expanded Disability Status Scale (EDSS) assessment, and a 3T MRI scan after 6,12 and 24 months, including the evaluation of white matter (WM) and cortical lesions (CLs). CSF levels of 67 inflammatory markers were assessed with immune-assay multiplex techniques. The 'no evidence of disease activity' (NEDA-3) status was assessed after two years and defined by no relapses, no disability worsening measured by EDSS and no MRI activity, including CLs. Results: Three patients were lost at follow-up. At the end of follow-up, 19 (48%) patients remained free from disease activity. IFNgamma, Chitinase3like1, IL32, Osteopontin, IL12(p40), IL34, IL28A, sTNFR2, IL20 and CCL2 showed the best association with disease activity. When added in a multivariate regression model including age, sex, and baseline EDSS, Chitinase 3 like1 (p = 0.049) significantly increased in those patients with disease activity. Finally, ROC analysis with Chitinase3like1 added to a model with EDSS, sex, age previous relapses, WM lesion number, CLs, number of Gad enhancing lesions and spinal cord lesions provided an AUC of 0.76 (95%CI 0.60-0.91). Conclusions: CSF Chitinase 3 like1 might provide prognostic information for predicting disease activity in the first years after initiation of cladribine. The drug's effect on chronic macrophage and microglia activation deserves further evaluation.

CORRELATION BETWEEN MICROPERIMETRY AND IMAGING IN EXTENSIVE MACULAR ATROPHY WITH PSEUDODRUSEN-LIKE APPEARANCE.

PURPOSE: To determine the correlation between microperimetry and imaging findings in extensive macular atrophy with pseudodrusen-like appearance (EMAP). METHODS: This cross-sectional, observational study included 44 consecutive patients with EMAP (88 eyes) and 30 healthy subjects (60 eyes). Both groups underwent visual acuity assessment, mesopic and scotopic microperimetry, fundus photography, autofluorescence, optical coherence tomography, and optical coherence tomography angiography. Retinal sensitivity was also subdivided in macular (0-4°) and paramacular areas (8-10°). Scotopic sensitivity loss was defined as the difference between scotopic and mesopic sensitivities for each tested point. Eyes with EMAP were further classified into the three stages described by Romano et al: 19 eyes in Stage 1, 31 in Stage 2, and 38 in Stage 3. RESULTS: Mesopic and scotopic retinal sensitivity were significantly reduced in patients with EMAP compared with controls, particularly in the macular area (all P < 0.001). Mesopic retinal sensitivity progressively declined in more advanced EMAP stages (all P < 0.01), but no scotopic differences were observed between Stages 2 and 3 ( P = 0.08). Remarkably, scotopic sensitivity loss was significantly higher in Stage 1 ( P < 0.05).On multivariate analysis, mesopic dysfunction was associated with larger atrophic areas ( P < 0.01), foveal involvement ( P = 0.03), and fibrosis ( P = 0.02). Conversely, no independent variable was associated with a reduced scotopic retinal sensitivity (all P > 0.05). CONCLUSION: The findings highlight that patients with EMAP suffer from a severe cone- and rod-mediated dysfunction on microperimetry. The predominant rod impairment in the early cases (Stage 1) emphasizes the importance of dark-adapted scotopic microperimetry as a clinical end point and suggests defective transportation across the RPE-Bruch membrane complex in its pathogenesis.

Towards a Long-Read Sequencing Approach for the Molecular Diagnosis of RPGRORF15 Genetic Variants.

Sequencing of the low-complexity ORF15 exon of RPGR, a gene correlated with retinitis pigmentosa and cone dystrophy, is difficult to achieve with NGS and Sanger sequencing. False results could lead to the inaccurate annotation of genetic variants in dbSNP and ClinVar databases, tools on which HGMD and Ensembl rely, finally resulting in incorrect genetic variants interpretation. This paper aims to propose PacBio sequencing as a feasible method to correctly detect genetic variants in low-complexity regions, such as the ORF15 exon of RPGR, and interpret their pathogenicity by structural studies. Biological samples from 75 patients affected by retinitis pigmentosa or cone dystrophy were analyzed with NGS and repeated with PacBio. The results showed that NGS has a low coverage of the ORF15 region, while PacBio was able to sequence the region of interest and detect eight genetic variants, of which four are likely pathogenic. Furthermore, molecular modeling and dynamics of the RPGR Glu-Gly repeats binding to TTLL5 allowed for the structural evaluation of the variants, providing a way to predict their pathogenicity. Therefore, we propose PacBio sequencing as a standard procedure in diagnostic research for sequencing low-complexity regions such as RPGRORF15, aiding in the correct annotation of genetic variants in online databases.

Unveiling the Hidden: Early Manifestations of Extensive Macular Atrophy with Pseudodrusen-like appearance.

PURPOSE: To describe novel microperimetry and imaging findings in two patients affected by extensive macular atrophy with pseudodrusen-like appearance (EMAP) without signs of retinal pigment epithelium (RPE) atrophy. METHODS: Case series. Both patients underwent mesopic and dark-adapted two-color scotopic microperimetry, followed by multimodal imaging assessment including ultra-widefield photography, fundus autofluorescence (AF), high-resolution optical coherence tomography (Hi-Res OCT), OCT angiography and high-magnification module (HMM). RESULTS: Albeit normal visual acuity, both patients had a significant reduction of retinal sensitivity - especially under scotopic cyan conditions. One patient had macular pigment abnormalities, while the combination of blue and near-infrared AF modalities highlighted different patterns of pseudodrusen-like lesions.Of notice, Hi-Res OCT revealed a marked separation between the RPE and Bruch's membrane, containing a hyperreflective material with two different reflectivities. OCT angiography excluded the presence of macular neovascularization and documented several choriocapillaris flow voids. HMM images showed severe alteration of photoreceptors' mosaic in the perifovea. CONCLUSIONS: Our comprehensive assessment of two stage 1 EMAP patients revealed a predominant damage of perifoveal rods over areas of RPE-Bruch's membrane separation. These findings underscore the importance of basal laminar deposits in the initial stages of EMAP, contributing to a deeper understanding of its underlying mechanisms.

The Acute Optic Neuritis Network (ACON): Study protocol of a non-interventional prospective multicenter study on diagnosis and treatment of acute optic neuritis.

Optic neuritis (ON) often occurs at the presentation of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). The recommended treatment of high-dose corticosteroids for ON is based on a North American study population, which did not address treatment timing or antibody serostatus. The Acute Optic Neuritis Network (ACON) presents a global, prospective, observational study protocol primarily designed to investigate the effect of time to high-dose corticosteroid treatment on 6-month visual outcomes in ON. Patients presenting within 30 days of the inaugural ON will be enrolled. For the primary analysis, patients will subsequently be assigned into the MS-ON group, the aquapotin-4-IgG positive ON (AQP4-IgG+ON) group or the MOG-IgG positive ON (MOG-IgG+ON) group and then further sub-stratified according to the number of days from the onset of visual loss to high-dose corticosteroids (days-to-Rx). The primary outcome measure will be high-contrast best-corrected visual acuity (HC-BCVA) at 6 months. In addition, multimodal data will be collected in subjects with any ON (CIS-ON, MS-ON, AQP4-IgG+ON or MOG-IgG+ON, and seronegative non-MS-ON), excluding infectious and granulomatous ON. Secondary outcomes include low-contrast best-corrected visual acuity (LC-BCVA), optical coherence tomography (OCT), magnetic resonance imaging (MRI) measurements, serum and cerebrospinal fluid (CSF) biomarkers (AQP4-IgG and MOG-IgG levels, neurofilament, and glial fibrillary protein), and patient reported outcome measures (headache, visual function in daily routine, depression, and quality of life questionnaires) at presentation at 6-month and 12-month follow-up visits. Data will be collected from 28 academic hospitals from Africa, Asia, the Middle East, Europe, North America, South America, and Australia. Planned recruitment consists of 100 MS-ON, 50 AQP4-IgG+ON, and 50 MOG-IgG+ON. This prospective, multimodal data collection will assess the potential value of early high-dose corticosteroid treatment, investigate the interrelations between functional impairments and structural changes, and evaluate the diagnostic yield of laboratory biomarkers. This analysis has the ability to substantially improve treatment strategies and the accuracy of diagnostic stratification in acute demyelinating ON. Trial registration: ClinicalTrials.gov, identifier: NCT05605951.

Atypical myelin oligodendrocyte glycoprotein antibody-associated optic neuritis and acute demyelinating polyneuropathy after SARS-CoV-2 infection: Case report and literature review.

Post-infectious immune-mediated neurological complications of Sars-Cov-2 have been increasingly recognized since the novel pandemic emerged. We describe the case of a 74 years-old patient who developed a Myelin Oligodendrocyte Glycoprotein (MOG) antibody-associated unilateral retrobulbar optic neuritis a few weeks after paucisymptomatic COVID-19 disease and, subsequently, after the resolution of the optic neuritis, an acute inflammatory demyelinating polyneuropathy. So far, no cases of these two neurological manifestations have been reported in the same patient. We herein report a case characterized by both manifestations and review the accumulating literature regarding MOG antibody-associated disease following SarsCov-2 infection.

Microscopic corneal epithelial changes and clinical outcomes in simple limbal epithelial transplantation surgery after treatment with amniotic membrane eye drops (AMED): A case report.

Purpose: To describe the microscopic epithelial changes and the clinical outcomes of a patient treated with amniotic membrane eye drops (AMED) because of a persistent epithelial defect (PED) and a partial limbal stem cell deficiency (LSCD) after simple limbal epithelial transplantation (SLET) and deep anterior lamellar keratoplasty (DALK). Observations: A 72-year-old patient, who had previously undergone SLET and DALK due to a total LSCD, presented with a PED related to a partial LSCD, and was treated with AMED for one month. We evaluated the patient's visual acuity, the Oxford grading scale, the Wong-Baker Pain Rating Scale, and in vivo confocal microscopy, both at baseline and 3 months after the end of treatment. Visual acuity improved from 0.5 to 0.4 LogMAR, the Oxford grading scale changed from grade III to grade I and the Wong-Baker Pain Rating Scale from grade 4 to grade 1. The corneal surface, which initially showed conjunctival characteristics over approximately 50% of the whole area, consisted mainly (75%) of mature corneal epithelium 3 months after the end of treatment. Conclusions and importance: While improving symptoms and clinical characteristics, AMED was also able to restore the normal corneal epithelium's morphology in a case of partial LSCD after SLET and DALK.

CSF TNF and osteopontin levels correlate with the response to dimethyl fumarate in early multiple sclerosis.

Background: Disease activity in the first years after a diagnosis of relapsing-remitting multiple sclerosis (RRMS) is a negative prognostic factor for long-term disability. Markers of both clinical and radiological responses to disease-modifying therapies (DMTs) are advocated. Objective: The objective of this study is to estimate the value of cerebrospinal fluid (CSF) inflammatory markers at the time of diagnosis in predicting the disease activity in treatment-naïve multiple sclerosis (MS) patients exposed to dimethyl fumarate (DMF). Methods: In total, 48 RRMS patients (31 females/17 males) treated with DMF after the diagnosis were included in this 2-year longitudinal study. All patients underwent a CSF examination, regular clinical and 3T magnetic resonance imaging (MRI) scans that included the assessment of white matter (WM) lesions, cortical lesions (CLs) and global cortical thickness. CSF levels of 10 pro-inflammatory markers - CXCL13 [chemokine (C-X-C motif) ligand 13 or B lymphocyte chemoattractant], CXCL12 (stromal cell-derived factor or C-X-C motif chemokine 12), tumour necrosis factor (TNF), APRIL (a proliferation-inducing ligand, or tumour necrosis factor ligand superfamily member 13), LIGHT (tumour necrosis factor ligand superfamily member 14 or tumour necrosis factor superfamily member 14), interferon (IFN) gamma, interleukin 12 (IL-12), osteopontin, sCD163 [soluble-CD163 (cluster of differentiation 163)] and Chitinase3-like1 - were assessed using immune-assay multiplex techniques. The combined three-domain status of 'no evidence of disease activity' (NEDA-3) was defined by no relapses, no disability worsening and no MRI activity, including CLs. Results: Twenty patients (42%) reached the NEDA-3 status; patients with disease activity showed higher CSF TNF (p = 0.009), osteopontin (p = 0.005), CXCL12 (p = 0.037), CXCL13 (p = 0.040) and IFN gamma levels (p = 0.019) compared with NEDA-3 patients. After applying a random forest approach, TNF and osteopontin revealed the most important variables associated with the NEDA-3 status. Six molecules that emerged at the random forest approach were added in a multivariate regression model with demographic, clinical and MRI measures of WM and grey matter damage as independent variables. TNF levels confirmed to be associated with the absence of disease activity: odds ratio (OR) = 0.25, CI% = 0.04-0.77. Conclusion: CSF inflammatory markers may provide prognostic information in predicting disease activity in the first years after DMF initiation. CSF TNF levels are a possible candidate in predicting treatment response, in addition to clinical, demographic and MRI variables.

Autologous simple conjunctival epithelial transplantation for primary pterygium.

PURPOSE: To evaluate the feasibility of a new method of conjunctival transplantation to achieve recovery of the normal conjunctival epithelium over the bare sclera after pterygium excision and prevent its recurrence. METHODS: After excision of the primary pterygium, we performed simple conjunctival epithelial transplantation (SCET) in which we glued an amniotic membrane patch pre-loaded with tiny autologous conjunctival tissue fragments over the scleral defect. Slit-lamp evaluation was performed at 2 and 7-10 days, and then at 1, 3, 6, and 12 months after surgery, together with confocal microscopy at 3, 6, and 12 months. RESULTS: Surgical excision and SCET for nasal primary pterygium were performed in 6 eyes (6 patients). No graft detachment occurred. An inflammatory granuloma was excised without sequelae in one patient 2 months after surgery. No signs of recurrence or sight-threatening complications were recorded at 12 months, and in vivo confocal microscopy showed progressive expansion of the conjunctival cell population and formation of a clear corneal-conjunctival transition. CONCLUSIONS: SCET takes advantage of the ability of the amniotic membrane and conjunctival cells to renew. Outcomes after SCET are comparable to conventional conjunctival flap surgery and can be achieved in less surgical time and with less donor tissue to be removed.

Extended Depth of Focus Versus Monofocal IOLs in Patients With High Myopia: Objective and Subjective Visual Outcomes.

PURPOSE: To compare the objective and subjective outcomes between the extended depth of focus (EDOF) Mini Well intraocular lens (IOL) and the aspheric monofocal Mini-4-Ready IOL (both SIFI S.p.A.) in patients with high myopia. METHODS: In this prospective comparative study, 40 patients with high myopia (axial length ≥ 26 mm) were enrolled: 20 patients were bilaterally implanted with the EDOF Mini Well IOL (EDOF group) and 20 patients were bilaterally implanted with the Mini-4-Ready IOL (monofocal group). Three-month follow-up data included corrected and uncorrected distance visual acuity at 4 m and 80, 67, and 40 cm, defocus curves, subjective and objective contrast sensitivity, objective optical quality (calculated with Optical Quality Analysis System; Visiometrics SL), halometry, and reading performance. Subjective visual quality was evaluated with National Eye Institute Refractive Error Quality of Life Instrument 42 scores. RESULTS: All visual acuities were significantly better in the EDOF group (P ⩽ .04) except monocular and binocular uncorrected and corrected distance visual acuities for distance (P ≥ .50). Defocus curves for myopic and hyperopic values were better in the EDOF group (P ⩽ .05), apart from +0.50 to -0.50 D (P ≥ .16). Contrast sensitivity curves was worse in the EDOF group in the mesopic-with-glare condition (P ⩽ .04). No differences were found in halometric values (P ≥ .15) and OQAS outcomes (P ≥ .47). National Eye Institute Refractive Error Quality of Life Instrument 42 subscale scores were better for expectation, near vision, activity limitations, and dependence on correction in the EDOF group (P ⩽ .04). CONCLUSIONS: Intermediate and near visual acuities were better in the EDOF group than in the monofocal group, with a comparable visual quality index between groups. [J Refract Surg. 2022;38(3):158-166.].

The Role of Topical Povidone-Iodine in the Management of Infectious Keratitis: A Pilot Study.

The aim of this prospective explorative study was to evaluate the safety and the effectiveness of topical polyvinylpyrrolidone-iodine (PVP-I) administered during the time-to-results period for pathogen identification and susceptibility testing in patients with infectious keratitis (IK). A corneal swab (CS) for antimicrobial evaluation was performed at enrollment (T0) and topical 0.66%-PVP-I was administered until the laboratory results were available (T1). Ulcer and infiltrate areas and infiltrate depths were compared between T0 and T1 (i.e., time-to-result period). Patients were then shifted to a specific antimicrobial therapy and followed up until resolution of their infiltrates (Tlast-TL). Twenty-five eyes were enrolled, and none showed clinical worsening leading to protocol withdrawal. At T1, ulcer and infiltrate areas showed significant improvement in Gram-positive IK (n = 13-52%; p = 0.027 and p = 0.019, respectively), remained stable in fungal IK (n = 5-20%; both p = 0.98) and increased in those with Gram-negative bacteria (n = 4-16%; p = 0.58 and p = 0.27). Eyes with negative cultures (n = 3-12%) showed complete resolution at T1 and did not initiate any additional antimicrobial therapy. The administration of 0.66% PVP-I during the time-to-result period seems to be a safe strategy in patients with IK while often sparing broad-spectrum antimicrobial agents. In addition, it showed to be effective in eyes with a Gram-positive bacterial infection.

Longitudinal Study of Optic Disk Perfusion and Retinal Structure in Leber's Hereditary Optic Neuropathy.

Purpose: The purpose of this study was to evaluate optic disk perfusion and neural retinal structure in patients with subacute Leber's hereditary optic neuropathy (LHON) and LHON carriers, as compared with healthy controls. Methods: This study included 8 patients with LHON in the subacute stage, 10 asymptomatic carriers of a LHON-associated mitochondrial DNA mutation, and 40 controls. All subjects underwent measurement of the retinal nerve fiber layer (RNFL) thickness, the ganglion cell-inner plexiform layer (GCIPL) thickness using optical coherence tomography and optic disk microvascular perfusion (Mean Tissue [MT]) using laser speckle flowgraphy (LSFG). Patients were re-examined after a median interval of 3 months from the baseline visit. Results: LHON carriers had higher values of RNFL thickness, GCIPL thickness, and disk area than controls (P < 0.05), whereas MT was not different between the two groups (P = 0.936). Median MT and RNFL thickness were 32% and 15% higher in the early subacute stage of the disease than in controls (P < 0.001 and P = 0.001). MT declined below the values of controls during the late subacute stage (P = 0.024), whereas RNFL thickness declined later during the dynamic stage (P < 0.001). GCIPL thickness was lower in patients with LHON than in controls independently of the stage of the disease (P < 0.001). Conclusions: The high blood flow at the optic disk during the early subacute stage may be the consequence of vasodilation due to nitric oxide release as compensation to mitochondrial impairment. Optic disk perfusion as measured by LSFG is a promising biomarker for LHON diagnosis and monitoring as well as an objective outcome measure for assessing response to therapies.

Multiple evanescent white dot syndrome: clinical course and factors influencing visual acuity recovery.

OBJECTIVE: To report the demographics and the clinical course of patients with multiple evanescent white dot syndrome (MEWDS) and to investigate for those factors which influence visual acuity (VA) recovery. METHODS: This is a retrospective single-centre observational study. Electronic medical records and retinal imaging of patients with a diagnosis of MEWDS with a minimum follow-up of 3 months were reviewed. Patients were categorised into three groups according to the VA at presentation and at the last visit: group 1 >0.48 logarithm of the minimum angle of resolution (LogMAR), group 2 ≤0.48 and ≥0.18 LogMAR and group 3 <0.18 LogMAR. All patients had non-invasive multimodal imaging including optical coherence tomography, near-infrared reflectance imaging and blue fundus autofluorescence at presentation and during follow-up. RESULTS: A total of 51 eyes from 51 patients (41 women, mean age 29.8±7.8 years) were included. Significantly more patients presented in the autumn (X2=8.69, p=0.034). The percentage of eyes recovering vision to 0.0 LogMAR or better was 80.3% (41/51). Worse presenting vision and young age at presentation were independent significant predictive variables for poorer final VA (p=0.002 and p=0.02, respectively). No imaging features were significantly predictive of complete versus incomplete recovery, but disc hyperfluorescence on fluorescein angiography was more common in those with incomplete recovery. CONCLUSIONS: Although the majority of cases have a benign prognosis, the clinical spectrum of MEWDS includes incomplete visual recovery. In our series, poor presenting VA and young age were associated with poor VA outcome. Further study is warranted to confirm these findings.

Early corneal and optic nerve changes in a paediatric population affected by obstructive sleep apnea syndrome.

PURPOSE: The relation between OSAS and eye diseases is well known in adults, while very few and contradictory data can be found regarding paediatric ages. The aim of this study is to explore the early corneal, macular and optic nerve changes in paediatric patients with OSAS. METHODS: Prospective study that enrolled children aged ≥ 4 years referred to the Paediatric Pneumology Clinic in Verona for suspected obstructive sleep apnoea syndrome (OSAS) and investigated with the overnight respiratory polygraphy. Patients with apnoea-hypopnea index (AHI) > 1 were classified as OSAS, while those with AHI < 1 were classified non-OSAS. All patients underwent comprehensive eye examination including slit lamp, refraction, intraocular pression (Goldman applanation tonometry), corneal tomography (corneal astigmatism, corneal keratometry at the apex, surface asymmetry index, central corneal thickness and thinnest corneal thickness) and optical coherence tomography (central macular thickness, macular volume and retinal nerve fibre layer). RESULTS: Seventy-two children were enrolled in the study. The overall prevalence of OSAS was 48.6%. Statistically significant differences were found between OSAS and non-OSAS group for corneal asymmetry (0.9 ± 0.5 and 0.6 ± 0.3, respectively; p = 0.02), thinnest corneal thickness (551.8 ± 33.9 and 563.7 ± 32.5; p = 0.04), average retinal nerve fibre layer (102.8 ± 10.5 µm and 98.1 ± 12.3 µm; p = 0.012) and in nasal quadrant (76.2 ± 15.4 µm and 66.5 ± 12.6 µm; p = 0.0002). CONCLUSIONS: A comprehensive eye examination with corneal and optic nerve imaging showed early corneal and optic nerve changes in children newly diagnosed with OSAS. These could be prelude of the known ocular manifestations associated with OSAS in adult patients.

Unique Features of Posterior Ocular Involvement of Whipple's Disease in a Patient with No Gastrointestinal Symptoms.

PURPOSE: To describe posterior ocular involvement features of Whipple's disease (WD) in a patient with no gastrointestinal symptoms. METHODS: Retrospective case report. OBSERVATION: A 53-year-old man with a 2-year history of seronegative arthritis presented with bilateral intraocular inflammation, optic disc edema, and cystoid macular edema (CME) in the left eye. A diagnosis of noninfectious uveitis was made and oral prednisolone was started. Despite initial improvement, after 6 weeks, CME was found in both eyes. Because of the initial response, the anti-tumor necrosis factor agent Adalimumab was started. Twelve weeks after initiation of adalimumab, fundus examination revealed widespread dot-blot retinal hemorrhages and multifocal chorioretinal lesions at the posterior pole and mid-periphery. The chorioretinal lesions appeared as hyperreflective drusen-like deposits located in the sub-retinal pigment epithelium (RPE) space on the tomographic scan. WD was considered and confirmed by polymerase chain reaction test and duodenal biopsy. CONCLUSION: Posterior ocular involvement in WD may present with a wide clinical spectrum including intraocular inflammation and unique features of sub-RPE deposits, widespread retinal hemorrhages, and optic disc edema.

22†Renewal of conjunctival epithelium over amniotic membrane to perform autologous simple conjunctival epithelial transplantation (SCET): in vitro validation and results of clinical application for primary pterygium.

BACKGROUND: Transplantation of ex vivo cultured conjunctival cell layers, generated on amniotic membrane or other scaffolds, provides a viable option in treating heterogeneous ocular surface conditions. By comparison, cell therapy is costly, labour-intensive and subject to good manufacturing practice requirements and regulatory approval; no conjunctival cell-based therapy is currently available. Several techniques are available after primary pterygium excision to recover the ocular surface anatomy by restoring healthy conjunctival epithelium and preventing recurrence and complications. However, application of conjunctival free autograft or transpositional flap to cover the bared scleral area is limited when the conjunctiva are to be spared for future glaucoma filtering surgery, in patients with large or double-headed pterygia, in recurrent pterygia, or when the harvesting of donor conjunctival is precluded by scarring. AIM: To develop a simple technique to obtain expansion of the conjunctival epithelium when applied in vivo in diseased eyes. METHODS: We evaluated in vitro the best way of gluing conjunctival fragments over the AM, the efficiency of the fragments to generate conjunctival cell outgrowths, the molecular marker expression, and the feasibility of shipping preloaded AM.We performed simple conjunctival epithelial transplantation (SCET) in which we glued an amniotic membrane patch pre-loaded with autologous conjunctival tissue fragments over the scleral defect after pterygium excision and evaluated the recovery of the normal conjunctival epithelium and the disease recurrence up to 12 months after surgery. RESULTS: 65-80% of fragments generated outgrowth 48-72h after gluing, without differences between type of AM preparation and fragment size. Within 6-13 days, a full epithelium covered the surface of the amniotic membrane. Specific marker expression (Muc1, K19, K13, p63, ZO-1) was detected. The shipping test showed after 24h the 31% of the fragments glued over the AM epithelial side, compared to more than 90% of fragments stayed attached in the remaining conditions (stromal side, stromal without spongy layer, epithelial side without epithelium).Surgical excision and SCET for nasal primary pterygium were performed in 6 eyes/patients. No graft detachment and recurrence occurred within 12 months. In vivo confocal microscopy showed progressive expansion of the conjunctival cell population and formation of a clear cornea-conjunctiva transition. CONCLUSIONS: We established the most suitable conditions for a novel strategy based on in vivo expansion of conjunctival cells from conjunctival fragments glued over the AM. The application of SCET seems to be effective and replicable for the renewal of conjunctiva in patients requiring ocular surface reconstruction.

Features of Retinitis-like Lesions in Vitreoretinal Lymphoma.

Purpose: To describe the distinguishing features of retinitis-like lesions seen in vitreoretinal lymphoma (VRL) from viral and toxoplasma retinitis.Methods: In this multicenter, retrospective study, we reviewed charts and imaging of consecutive patients with VRL. The associated features and the characteristics of retinitis-like lesions were assessed and compared with those of viral and toxoplasmic retinochoroiditis. Primary outcome measures were the unique features of VRL retinitis-like lesions.Results: Out of 76 eyes of 38 patients with VRL, retinitis-like lesions were identified in 6 eyes and confirmed on OCT. Distinctive features of VRL retinitis-like lesions were massive retinal thickening, associated sub-retinal pigment epithelium infiltrates and partial restoration of retinal layers after specific therapy.Conclusion: VRL can present with retinitis-like lesions that have distinctive OCT features on presentation as well as healing that can help to differentiate them from other lookalike etiologies and can guide further diagnostic and therapeutic interventions.

Do behaviour change techniques increase adherence to home exercises in those with upper extremity musculoskeletal disorders? A systematic review.

OBJECTIVES: To investigate whether behaviour change techniques (BCTs) can influence adherence to home exercise in people with upper extremity musculoskeletal disorders (UEMD). DESIGN: A systematic review of randomised control trials, non-randomised control trials, case-control studies and cohort studies. Results were presented narratively. Participants were those with UEMD. The intervention was any home exercise programme, alongside a BCT designed to increase exercise adherence. Any duration of intervention was accepted. The main outcome sought was adherence to home exercise. A systematic search was performed on four online databases. Grey literature was searched. RESULTS: The search resulted in 28,755 titles. 77 full-text articles were assessed for eligibility. Six studies were included in the qualitative synthesis. Four studies had Some Concern of Bias, whilst two studies had High Risk of Bias. Three studies found statistically significant differences in exercise adherence (p < 0.05) between the Intervention group and Control group. The BCT 'Social Support (unspecified)' was used within all studies that found significant differences in adherence levels at outcome. However, multiple BCTs were received by the Intervention groups within all studies, making it impossible to identify the effects of any single BCT upon adherence levels. CONCLUSION: Social support may be relevant in patients' adherence levels to HEPs. However, confidence in the results is uncertain given the small number of studies found, and their High RoB. Future studies should validate their measurement and definition of adherence, as well as the number of BCTs they use, to provide reproducible evidence.

Very late recurrence of iris melanoma: 45 years after treatment.

Iris melanoma is a rare tumour that accounts for ~3-4% of all uveal melanoma cases. In the past, surgical resection was the sole treatement option, whereas nowadays, it has been replaced by brachytherapy as treatment of choice. Surgical resection is still in use in selected cases but combined with adjuvant radiotherapy in cases of incomplete resection. Herein, we report the case of a very late recurrence, 45 years after surgical resection. A literature review was performed to detect the latest recurrence reported to date and to understand the etiology behind very late recurrences. The role of multiple factors is discussed to explain this extremely delayed growth.