Following prevalence of myopia in a large Swiss military cohort over the last decade: where is the European "myopia boom"?

PURPOSE: Myopia prevalence is increasing globally, with the highest rates found in Asia. Data from European countries is scarce. We aimed to investigate whether the prevalence of myopia is rising in our meridians. METHODS: Data from male military conscripts for the recruitment period of 2008-2017 were retrospectively analyzed. Year of recruitment, conscripts' birth year, visual acuity, refractive status (spherical equivalent), and spectacle wear (yes/no) were available. RESULTS: The dataset contained data of a total of 355,657 male conscripts, who had been recruited in the years 2008 to 2017. The mean number of conscripts per year was 35,566 (MD = 35,440, SD = 1249), reaching a minimum number of 33,998 conscripts in 2017 and a maximum of 37,594 in 2011. Mean age at recruitment was 19.7 years (MD = 19.0 years, SD = 1.1 years). Overall, the number of conscripts wearing spectacles remained stable over the observation time; on average 29.6% (n = 10,540; MD = 10,472; SD = 492) of conscripts wore glasses at recruitment. Of 21.8% (n = 77,698) of conscripts, data on the refractive status was available: The mean spherical equivalent for both right and left eyes was -2.3D (MD = -2 D, SD = 2.4 D). No decrease in mean spherical equivalent per recruitment year was noted over the observation period. Estimated myopia prevalence reached an average of 27.5% (SD = 0.8%) and did not increase during the observation period. CONCLUSION: In summary, no change in spherical equivalent refractive errors of male Swiss army conscripts was found for the years 2008-2017. Equally, the percentage of spectacle wearers (MN = 29.6%) and estimated myopia prevalence (MN = 27.5%) did not significantly increase during the observation time. TRIAL REGISTRATION:  BASEC 2019-00060 (18/01/2019).

Electrodiagnostic Biomarkers in Paraneoplastic Retinopathy.

OBJECTIVE: Paraneoplastic retinopathy (PNR) is a rapid-onset photoreceptor and post-photoreceptor dysfunction triggered by a cross-reaction between antigens expressed by the underlying tumour and retinal proteins. The present study aims to determine the electrodiagnostic biomarkers that support the diagnosis of PNR and evaluate the effect of treatment. METHODS: A retrospective observational case-controlled study including 25 patients with suspected PNR, of which 11 patients were diagnosed with PNR. The presence of PNR was confirmed based on clinical examination, supported by colour fundus photography, fundus autofluorescence imaging, optical coherence tomography, fluorescein angiography, retinal vessel oximetry, colour test, full-field electroretinogram (ffERG), on-/off ERG, S-cone ERG, and multifocal ERG (mfERG). The relationships between the clinical symptomatology and the effect of therapy were evaluated. RESULTS: All PNR patients (Nr: 11) presented with subjective symptoms of newly reported central vision or visual field deterioration. Posterior segment findings showed a severe patchy-like retinal atrophy, attenuation of the retinal vessels, and a waxy optic disc. Optical coherence tomography revealed a discontinued ISe line, and multiple hyperreflective foci. Retinal vessel oxygen saturation was increased. Multifocal ERG revealed reduced central and paracentral responses and ffERG severely attenuated scotopic-, photopic-, on-/off- and S-cone responses. The colour vision test revealed a tritan-tetartan-weakness. Two of the PNR patients underwent rituximab therapy with no further progression and even recovery of electrodiagnostic responses.In 1 nPNR (non-paraneoplastic retinopathy) patient (total Nr: 14) pseudoxanthoma elasticum-related retinopathy was the reason for impaired vision. In 3 of 13 patients with bronchopulmonary cancer a MEK- and FGFR-inhibitor- drug toxicity was the reason for the visual deterioration. CONCLUSION: Careful investigation for signs of central and/or peripheral visual field deterioration must be performed in the presence of history of a co-existing malignancy. The possibility of PNR should be taken into account. The electrodiagnostic biomarkers, suggested in this study, may help to promptly recognise PNR and also to evaluate the effect of implemented therapy.

Influence of Post-radiation Ocular Surface Disorder on Ocular Surgery: A Case Report and Review of the Literature.

BACKGROUND: Ocular surface disorder after ocular radiation therapy, even though commonly reported, is often overlooked. Any delay in diagnosis may lead to complications that threaten vision. The presented case highlights the clinical outcome of a severe post-radiation disorder of the ocular surface, the importance of intensive therapy, and the limitations of further surgical interventions. CASE PRESENTATION: A 34-year-old woman was referred for a second opinion due to a years-long history of pain and redness in her right eye (OD) after proton beam therapy for recurrent iris melanoma. The patient then developed post-radiation retinopathy with macula edema, secondary glaucoma, cataract, as well as a severe ocular surface disorder with corneal decompensation and band keratopathy. Several surgical treatments have been attempted, including phacoemulsification with IOL implantation and trabeculectomy with mitomycin C. Due to refractory glaucoma, Baerveldt glaucoma drainage was then necessary. Given the worsening clinical presentation of post-radiation ocular surface disorder with progressing band keratopathy, the possibility of penetrating keratoplasty (PKP) was discussed. CONCLUSION: The continuous worsening of clinical symptoms of the disorder of the ocular surface after proton beam radiotherapy can be the result of a post-radiation syndrome. Gradual expansion of ischemia, vasculitis, and inflammatory mediators compresses the retinal tissue, leading to recurrent macular edema as well as to secondary glaucoma and corneal decompensation. Band keratopathy is occasionally noted and seems to result from severe post-radiation disorder of the ocular surface. However, PKP would typically be indicated in cases of corneal perforation, uncontrolled infectious keratitis, or for improving vision in the presence of corneal opacification, none of which applied to our patient. Furthermore, post-radiation keratopathy implies compromised corneal stromal lymphogenesis and angiogenesis, both of which are now considered essential conditions for allograft rejection. Moreover, a previously performed Baerveldt glaucoma drainage surgery can affect the survival rate of the endothelial cells of the recipient cornea. Therefore, a penetrating or endothelial keratoplasty should be viewed as a high-risk procedure. In this instance, the rigorous treatment of the severe ocular surface disorder was crucial. We managed our patient's complex situation by following the latest guidelines set by the Tear Film & Ocular Surface Society and aimed to alleviate the symptoms as effectively as possible. In conclusion, careful decision-making regarding surgical treatment options should be considered, taking into account the complexities and potential risks involved.

Morphology of Serous Retinal Detachment in Morning Glory Optic Disc Anomaly in a Patient before and after Treatment with Systemic Carboanhydrase Inhibitors.

BACKGROUND: Morning glory optic disc anomaly (MGODA) is a rare congenital defect of the optic nerve head. The optic nerve is enlarged, and its conical excavation is filled with glial tissue. It may be associated with cerebral malformations and ocular complications, whereas serous retinal detachment occurs in 38% of affected patients. Surgical treatment of detachment showed poor visual outcome in the past and conservative treatment options are scarce. CASE: A woman with MGODA presented in our clinic with sudden vision loss due to serous retinal detachment. She denied any previous ophthalmological problems and her past medical history was unremarkable. Vision testing showed normal visual acuity in her left eye and finger counting in her right eye. Slit lamp examination was unremarkable. Fundus examination of the right eye showed retinal detachment without holes or traction membranes and an enlarged optic disc with raised peripapillary tissue and glial tissue in the center of the optic disc. Due to the pathognomonic otpic disc finding, we diagnosed MGODA complicated by a serous retinal detachment. We treated the patient with systemic carboanhydrase inhibitors and documented the initial clinical findings as well as the course of disease under treatment by optical coherent tomography (OCT), fundus autofluorescence imaging (FAF), and visual field testing. During follow-up, we detected noticeable subretinal fluid regression and improvement in visual acuity. CONCLUSION: The application of oral carboanhydrase inhibitors appears to be a valid therapeutic option in patients with MGODA-associated serous macular detachment. OCT and FAF imaging are useful modalities for documentation of subretinal fluid regression and structural changes in the peripapillary region.

Clinical Heterogeneity in Two Siblings Harbouring a Heterozygous PRPH2 Pathogenic Variant.

PURPOSE: The aim of the study was to describe the clinical and genetic correlation of a c.469 G>A p.(Asp157Asn) heterozygous pathogenic variant in PRPH2 in two siblings of Italian origin. PATIENTS AND METHODS: Both patients underwent ophthalmic examination, electrophysiological testing, autofluorescence imaging, and optical coherence tomography (OCT). Screening for pathogenic variants of the obtained DNA from the family members was carried out. RESULTS: The 52-year-old (♀, index patient) and 50-year-old (♂) siblings had BCVA (OD and OS) of 20/20 and 20/16 (♀) and 20/25 and 20/40 (♂), respectively, and suffered increased sensitivity to glare. Yellow irregular macular deposits, numerous small irregular hypo- and hyperreflective spots at the posterior pole, a patchy loss of photoreceptors, and retinal pigment epithelium (RPE) in the perifoveal region were seen. Electrophysiology showed dysfunction of rods and cones, with more affected cone dysfunction in the index patient, contrary to the generalised rod dysfunction in the brother of the index patient. The clinical, electrophysiological, and multimodal imaging findings of both siblings pointed towards Stargardt retinopathy with heterogenic presentation. The DNA analysis identified an autosomal dominant c.469 G>A p.(Asp157Asn) heterozygous pathogenic variant in PRPH2 associated with autosomal dominant cone-rod dystrophy and rod-cone dystrophy. PRPH2 codes for peripherin-2, a membrane protein that consists of 346 amino acids. CONCLUSIONS: Our findings confirm a heterogeneity in clinical presentation associated with pathogenic variants in PRPH2. It may follow either an autosomal dominant or an autosomal recessive mode of inheritance and show a very heterogeneous clinical manifestation of retinal degeneration, e.g., autosomal dominant retinitis pigmentosa (♂ sibling; II-3) and autosomal dominant cone-rod dystrophy (index ♀ sibling; II-2), autosomal dominant macular dystrophy, and also autosomal recessive retinitis pigmentosa.

Analysis of Suspected Achromatopsia by Multimodal Diagnostic Testing.

BACKGROUND: Achromatopsia (ACHM) as a hereditary cone disease might manifest in a stationary and progressive manner. The proper clinical and genetic diagnosis may allow an individual prognosis, accurate genetic counselling, and the optimal choice of low vision aids. The primary aim of the study was to determine the spectrum of clinical and genetic diagnostics required to characterize the ACHM. METHODS: A retrospective analysis was performed in 8 patients from non-related families (5 ♀,3 ♂); age at diagnosis: 3 - 56 y, mean 18.13 (SD ± 18.22). Clinical phenotyping, supported by colour vision test, fundus photography-, autofluorescence- (FAF), infra-red- (IR), OCT imaging and electroretinography provided information on the current status and the course of the disease over the years. In addition, genetic examinations were performed with ACHM relevant testing (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H and the transcription factor ATF6). RESULTS: All patients suffered photophobia and reduced visual acuity (mean: 0.16 [SD ± 0.08]). Nystagmus was identified in 7 from 8 subjects and in one patient a head-turn right helped to reduce the nystagmus amplitude. Colour vision testing confirmed complete achromatopsia in 7 out of 8 patients. Electrophysiology found severely reduced photopic- but also scotopic responses. Thinning and interruption of the inner segment ellipsoid (ISe) line within the macula but also FAF- and IR abnormalities in the fovea and/or parafovea were characteristic in all ACHM patients. Identification of pathogenic mutations in 7 patients helped to confirm the diagnosis of ACHM (3 adults, 4 children; 3 ♀ and 4 ♂). Achromatopsia was linked to CNGA3 (2 ♀, 1 ♂) and CNGB3 variants (2 ♀, 3 ♂). The youngest patient (♀, 10 y) had 3 different CNGB3 variants on different alleles. In a patient (♂, 29 y) carrying 2 pathogenic digenic-triallelic CNGA3- and CNGB3-mutations, a severe progression of ISe discontinuity to coloboma-like macular atrophy was observed during the 12-year follow-up. The oldest female (67 y) showed a compound homozygous CNGA3- and heterozygous CNGB3-, as well as a heterozygous GUCY2D variants. The destruction of her ISe line was significantly enlarged and represented a progressive cone-rod phenotype in comparison to other ACHM patients. In a patient (♂, 45 y) carrying a pathogenic CNGB3 and USH2 mutation, a severe macular oedema and a rod-cone phenotype was observed. In addition, two variants in C2ORF71 considered as VOS were found. One patient showed the rare ATF6 mutation, where a severe coloboma-like macular atrophy was observed on the left eye as early as at the age of three years. CONCLUSION: Combining multimodal ophthalmological diagnostics and molecular genetics when evaluating patients with ACHM helps in characterizing the disease and associated modifiers, and is therefore strongly recommended for such patients.

Contribution of Whole-Genome Sequencing and Transcript Analysis to Decipher Retinal Diseases Associated with MFSD8 Variants.

Biallelic gene defects in MFSD8 are not only a cause of the late-infantile form of neuronal ceroid lipofuscinosis, but also of rare isolated retinal degeneration. We report clinical and genetic data of seven patients compound heterozygous or homozygous for variants in MFSD8, issued from a French cohort with inherited retinal degeneration, and two additional patients retrieved from a Swiss cohort. Next-generation sequencing of large panels combined with whole-genome sequencing allowed for the identification of twelve variants from which seven were novel. Among them were one deep intronic variant c.998+1669A>G, one large deletion encompassing exon 9 and 10, and a silent change c.750A>G. Transcript analysis performed on patients' lymphoblastoid cell lines revealed the creation of a donor splice site by c.998+1669A>G, resulting in a 140 bp pseudoexon insertion in intron 10. Variant c.750A>G produced exon 8 skipping. In silico and in cellulo studies of these variants allowed us to assign the pathogenic effect, and showed that the combination of at least one severe variant with a moderate one leads to isolated retinal dystrophy, whereas the combination in trans of two severe variants is responsible for early onset severe retinal dystrophy in the context of late-infantile neuronal ceroid lipofuscinosis.

Two-Year Outcome of Surgery in Glaucoma Patients.

PURPOSE: To evaluate the 2-year surgical treatment outcome in glaucoma patients. METHODS: A retrospective, single-center, interventional study was performed on 160 eyes of 125 patients suffering glaucoma, including POAG (82 eyes), pseudoexfoliation (PEX) (59 eyes), pigment dispersion (8 eyes), and secondary glaucoma (2 eyes). Eyes with uncontrolled intraocular pressure (IOP) or signs of glaucoma progression despite medical treatment were included to undergo either trabeculectomy (TE), XEN implantation, combined TE with phacoemulsification (TE + IOL), or XEN implantation with phacoemulsification surgery (XEN + IOL). Primary efficacy outcome was the mean IOP reduction. Secondary outcome was the mean reduction in the number of medications. The data were compared at baseline vs.1 day, 1 week, and 1, 3, 6, 12, and 24 months following surgery. For statistical evaluation, ANOVA-based linear mixed-effects models were performed with SPSS. RESULTS: The mean IOP reduction in a 2-year follow-up was 30.31% (22.17 vs. 15.45 mmHg, p < 0.001). The mean number of antiglaucoma medications was reduced from 2.87 to 0.58 (p = 0.001), where TE alone or combined surgeries seemed to be more effective than isolated XEN surgery. Transient IOP hypotony on the first postoperative day occurred in PEX patients following TE surgery (p = 0.024). At 6 months, PEX patients with isolated XEN surgery showed a transient IOP increase, whereas those after combined TE + IOL surgery showed the lowest IOP within the PEX group compared to other glaucoma patients (p < 0.026). CONCLUSIONS: After 2 years, all performed glaucoma surgeries achieved a significant reduction in IOP and the number of antiglaucoma medications.

Structural, Microvascular, and Functional Findings Associated with Fovea Plana.

PURPOSE: To analyse structural (OCT), microvascular (OCTA), and functional changes (BCVA, mfERG) associated with fovea plana and to compare it to healthy controls. METHODS: A retrospective observational study was performed on 13 patients (26 eyes; aged 34.46 y ± 20.26) with a clinical picture of fovea plana and 15 controls (30 eyes; aged: 41.47 y ± 14.03). RESULTS: In fovea plana, BCVA ranged from 0.25 to 1.0, with a spherical error of - 5.5 to + 18.0 dpt. Posterior segment changes included elevated papillomacular retinal fold, uveal effusion syndrome, crowded optic discs, and hypopigmented fundus. OCTA imaging of the superficial (FAZ-S), intermediate (FAZ-I), and deep foveal avascular zone (FAZ-D) confirmed absence of foveal avascular zone (FAZ-S in 13 eyes, FAZ-I in 21 eyes, and FAZ-D in 10 eyes). Fovea plana patients had a significantly smaller FAZ-S, FAZ-I, and FAZ-D than controls (p < 0.001). Within the fovea plana group, a smaller FAZ-S correlated with reduced BCVA (p = 0.004) and with reduced mfERGs in zones 1 and 2 (p = 0.001 and p = 0.017). Also, a smaller FAZ-D showed positive correlations with the mfERG, with statistically significant values in zones 1 and 2 (p = 0.003 and p = 0.017). CONCLUSION: In conclusion, our results confirm an altered structural, microvascular, and functional pattern in patients with a clinical picture of fovea plana. As documented by the functional microvascular interactions in our study, the developmental arrest in foveation reflects the functional maturation by means of visual acuity and central retinal function.

The impact of macular edema on microvascular and metabolic alterations in retinitis pigmentosa.

PURPOSE: The primary aim of our study was to evaluate retinal microvascular anomalies recorded with optical coherence tomography angiography (OCTA) and the retinal metabolic function measured with retinal oximetry (RO) in patients with retinitis pigmentosa (RP). The secondary aim of the study was to link the presence of macular edema to microvascular and metabolic parameters in RP. METHODS: OCTA and RO were performed on 94 eyes: 64 eyes diagnosed with RP with (ME-RP) and without (no-ME-RP) macular edema were compared with 30 control eyes. Study end points were as follows: mean superficial (FAZ-S) and deep foveal avascular zone (FAZ-D) determined by OCTA. In addition, we evaluated the mean arterial (A-SO2; %), venular (V-SO2; %) oxygen saturation, their difference (A-V SO2; %), as well as the corresponding mean diameter of the retinal arterioles (D-A; µm) and venules (D-V; µm). RESULTS: RP patients differed from controls by enlarged FAZ-S and FAZ-D (p ≤ 0.001), attenuated retinal vessels (p ≤ 0.001), and increased retinal vessel oxygen saturation (p ≤ 0.010). Subgroup analyses within RP patients revealed more pronounced alterations of microvascular parameters and metabolic function in the presence of macular edema. In the no-ME-RP subgroup, significant interactions were present between FAZ-S, A-SO2, and V-SO2, whereas in the ME-RP subgroup, we found significant correlations between FAZ-D and D-A. CONCLUSION: A combined microvascular structure-metabolic function approach enhances our understanding of inherited retinal diseases. The presence of macular edema in RP seems to be a result of more altered microvascular-metabolic function. Macular edema should thus be taken into consideration when evaluating microvascular and/or metabolic changes in RP.

[Nishida Extraocular Muscle Transposition Surgery for Abducens Nerve Palsy]. / Augenmuskeltransposition nach Nishida bei Abduzensparese.

BACKGROUND: Surgical treatment of abducens nerve palsy depends on the remaining function of the lateral rectus muscle. Vertical rectus transposition surgery is indicated if the attempted maximal abduction effort does not rotate the eye beyond the midline. After the first description more than 100 years ago, a variety of muscle transposition modifications have been suggested. Nishida's minimally-invasive adaptation has attracted a great deal of attention in recent years. PATIENTS AND METHODS: Retrospective case series of four patients with abducens nerve palsy who were treated with Nishida muscle transposition surgery. Patients' characteristics with special emphasis on comparison between pre- and postoperative angle of deviation and ocular motility are reported. RESULTS: Four patients (2 females, 2 males) were included in this study. Unilateral transposition surgery was performed in a 7-year-old girl and a 37-year-old woman with a left abducens nerve palsy. In a 56-year-old male with a left sixth nerve palsy and in an 82-year-old male with a right sixth nerve palsy the transposition maneuver was combined with a recession of the medial rectus muscle in the same eye. In all patients, ocular motility was improved and the angle of deviation was reduced. CONCLUSIONS: Transposition of vertical rectus muscles is well established in the surgical treatment of abducens nerve palsy. Nishida's adaptation is a safe, effective and minimally-invasive treatment option. This vessel-sparing technique also allows for equilateral weakening of the medial rectus muscle.

Optic Disc Features in Familial Retinal Arteriolar Tortuosity.

PURPOSE: Describing optic disc appearance in familial retinal arteriolar tortuosity (fRAT) using multimodal imaging and raising awareness of peripapillary arterial changes due to this disorder. METHODS: A cross-sectional study was performed in four consecutive patients of two non-related families. Detailed ophthalmological examination was performed and supported by medical and family history and multimodal imaging. RESULTS: In all subjects, increased tortuosity of second- and third-order retinal arteries in superior and deeper vascular plexus was documented. Furthermore, tortuosity in the peripapillary circle of Zinn-Haller was found. In addition, retinal vessel oximetry confirmed tortuosity only of the arterial vessels. CONCLUSION: The present data suggests that a blurry bordered, hyperemic optic disc in the presence of abnormally tortuous arteriolar vessels and asymptomatically or oligosymptomatically spontaneously resolved hemorrhages could be associated with a fRAT. This finding could be linked to peripapillary arterial vessel tortuosity.

Drug-Induced Pseudo-Central Serous Chorioretinopathy in Carcinoma Patients.

PURPOSE: Patients with carcinomas often share symptoms of vision deterioration as part of paraneoplastic retinopathy (PNR), based on a cross-reaction between antigens expressed by the underlying tumor and retinal proteins. However, some of the underlying symptoms may be explained by a drug-induced toxicity. The application of new therapeutic strategies with mitogen-activated protein kinase (MEK) and fibroblast growth factor receptor (FGFR) inhibitors in advanced cancers are still under evaluation for safety and tolerability, but also for dose-limiting toxicities. In the presented data, we identified a drug-induced pseudo-central serous chorioretinopathy (pCSC) to be the reason for central vision deterioration. METHODS: A retrospective, observational, case-controlled study included seven patients receiving MEK and six patients receiving FGFR inhibitor treatment for bronchopulmonal cancer. We compared the clinical and diagnostic pictures of pCSC patients with that of 50 CSC patients (100 eyes) and 7 patients (14 eyes) with PNR. The activity of pCSC was assessed by clinical examination, supported by multimodal imaging. The relationships between clinical symptomatology and systemic disease activity were evaluated. RESULTS: Three out of thirteen patients (23.1%) showed signs of pCSC (one FGFR and two MEK inhibitor patients). All three pCSC patients showed central bilateral detachment of the neurosensory retina on OCT imaging, but also paracentral multifocal lesions in the second subject. Compared to our CSC and PNR patients, the lesions in pCSC patients showed no lipofuscin irregularities on FAF. With reduction of the MEK treatment, the lesions on one MEK subject disappeared and BCVA restored to 0.8. In one MEK- and the FGFR subject, the lesions reduced in size without therapy discontinuation. CONCLUSION: Based on our data, MEK and FGFR inhibitor-associated pCSC is a mild, self-limited retinopathy that seems to disappear simultaneously or shortly after discontinuation of medication, with subsequent restoration of the central visual function.

Linking the Presence of Macular Oedema to Structural and Functional Alterations in Retinitis Pigmentosa.

OBJECTIVE: To investigate the association between the central retinal thickness (CRT), the retinal nerve fibre layer thickness (RNFL), and the functional alterations in retinitis pigmentosa (RP) patients. METHODS: Forty-three patients with typical RP and nineteen age-matched controls, who underwent SD-OCT (macular and optic disc OCT protocols) and electrophysiology, were included. The RP group was divided into two subgroups: with clinical appearance of macular oedema (ME-RP; 30 eyes) and without macular oedema (no-ME; 44 eyes). Central retinal thickness OCT data were averaged in three zones (zone 1 [0°-3°], zone 2 [3°-8°], and zone 3 [8°-15°]) and were evaluated in relation to the RNFL thickness and electrophysiological data. RESULTS: The ME-RP group showed increased CRT (zone 1) and RNFL thickness compared to the controls and no-ME-RP (p ≤ 0.002). The no-ME-RP group had reduced CRT thickness (all zones; p ≤ 0.018) compared to the controls and ME-RP, whereas the RNFL thickness in the no-ME-RP group was reduced only compared to the ME-RP group (p < 0.001). The ME-RP group showed significantly more attenuated functional responses than the no-ME-RP patients. A significant positive interaction was found between the CRT (zones 1 and 2) and the RNFL thickness within ME-RP (p ≤ 0.010). Significant negative interactions were found between CRT, RNFL thickness, and functional findings within ME-RP (p ≤ 0.049). CONCLUSION: The presence of macular oedema correlated well with increased RNFL thickness and residual function in RP patients. Such association provides evidence of an underlying transneuronal mechanism of retinal degeneration. Simultaneous monitoring of CRT and RNFL thickness may help in the future to evaluate the progression of the disease and the efficacy of treatments in RP patients.

Metabolic monitoring of transcorneal electrical stimulation in retinitis pigmentosa.

PURPOSE: Transcorneal electrical stimulation (TES) is a novel treatment approach for patients with retinitis pigmentosa (RP). With progression of RP, loss of photoreceptors leads to less oxygen consumption and lower demand in the retina. Retinal oximetry (RO), as a non-invasive method to analyse oxygen saturation in retinal vessels, promises to be a useful therapy monitoring tool. The aim of our study was to observe changes in RO that would be attributed to therapeutic intervention. METHODS: A total of 43 eyes of 22 subjects (11♀ 11♂) suffering from RP were examined at baseline, after the first stimulation, 1 week and 6 months after TES (OkuStim®). Stimulation was performed for 30 min weekly at 200% of the individual phosphene threshold, simultaneously on both eyes. The oxygen saturation was examined at baseline and following TES stimulation with the oxygen saturation tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). The global oxygen saturation parameters (in %), within 1.0-1.5 optic disc diameters from the disc margin, in retinal arterioles (A-SO2) and venules (V-SO2) were estimated and their difference (A-V SO2) was calculated. In addition, we evaluated the diameters (in µm) in the corresponding arterioles (D-A) and venules (D-V). ANOVA-based linear mixed-effects models were calculated with SPSS®. RESULTS: Six months after TES treatment, the mean A-SO2 increased (from 96.48 ± 12.27 to 100.15 ± 5.56%, p = 0.09), while the V-SO2 decreased (from 61.61 ± 12.78 to 59.79 ± 11.15%, p = 0.48). The A-V SO2, which represents the oxygen consumption of the retina, showed a statistically significant increase from 34.87 ± 9.38% at baseline to 41.36 ± 9.18% after 6 months (p = 0.02). TES had no influence on the D-A and D-V (p > 0.6). CONCLUSION: These data indicate that TES therapy in RP leads to an increased oxygen consumption of the retina. RO may thus serve as a sensitive monitoring method for TES therapy in RP.

First Clinical Experience with Anti-myelin Oligodendrocyte Glycoprotein Antibody-Positive Optic Neuritis.

BACKGROUND: Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been consistently found in a range of demyelinating disorders. In this context, MOG-IgG-associated optic neuritis (ON) has been suggested as a new subset of optic neuropathy. However, clinical manifestations and distinctive characteristics have only rarely been described. PATIENTS AND METHODS: A retrospective case series of three patients with MOG-IgG-associated ON. Clinical morphological features using imaging techniques are presented. RESULTS: Three patients (8-year-old boy, 28-year-old female, 48-year-old male) were included. An 8-year-old boy suffered from a bilateral ON with severe visual loss. The best-corrected visual acuity (BCVA) was 0.05 in the right eye and finger counting in the left eye. The patient had a previous episode of acute disseminated encephalomyelitis (ADEM) with a right abducens nerve palsy. Visual acuity recovered after repeated cycles of intravenous methylprednisolone pulse therapy and 10 cycles of plasma exchange. During the last follow-up, BCVA was 0.9 in the right eye and 0.8 in the left eye. A 28-year-old female presented with a bilateral ON. Her BCVA was 0.5 in the right eye and 0.8 in the left eye. She fully recovered with pulse methylprednisolone therapy (1000 mg/d) with tapering after the second cycle and had a BCVA of 1.0 during the last follow-up visit. A 48-year-old male suffered from a relapsing bilateral ON. At first presentation, BCVA was 0.1 in the right eye and finger counting in the left eye. BCVA fully recovered after each pulse therapy with intravenous methylprednisolone (two cycles). Since the first relapse, the patient has been receiving long-term immunosuppression with rituximab. Despite rituximab and low-dose oral prednisone, the patient had another relapse with a left ON. After a third cycle with intravenous methylprednisolone, he partially recovered. BCVA at last follow-up was 1.0 in the right and 0.8 in the left eye. CONCLUSIONS: MOG-IgG antibodies have been identified in different acquired demyelinating syndromes. The patients reported had an ADEM followed by bilateral ON, an isolated bilateral ON, and a relapsing bilateral ON. Individual treatment strategies led to substantial visual recovery in all patients. We recommend inclusion of MOG-IgG antibodies in the diagnostic workup at least after the first recurrence of ON since they can serve as a diagnostic and potential prognostic tool and might lead to specific therapeutic recommendations.

Choroidal Manifestation of Systemic Non-Tuberculous Mycobacterial Infection: A Case Series.

PURPOSE: To describe choroidal findings associated with disseminated systemic non-mycobacterial infection. METHODS: A retrospective observational case series included two patients (four eyes) with non-tuberculous mycobacterial disease. The activity of choroidal lesions was assessed by clinical examination, supported by colour fundus photography, fundus autofluorescence imaging, indocyanine green angiography, fluorescence angiography, and optical coherence tomography (OCT) angiography. The relationships between clinical symptomatology, choroidal findings, and systemic disease activity were evaluated. RESULTS: One subject diagnosed with aortic graft infection showed positive cultures for Mycobacterium chimaera. One HIV-positive subject showed a positive saliva culture for Mycobacterium avium. At presentation, all subjects showed chorioretinal manifestation. In one patient, the lesions were active and in the other patient, the lesions appeared inactive. With activity of disseminated chorioretinitis, the lesions had indistinct, blurred borders on fluorescence angiography and indocyanine green angiography and were hyporeflective with well-defined borders on OCT imaging. CONCLUSION: Multimodal imaging enables distinction between active and inactive lesions, thus supporting therapeutic management. Choroidal presentation of active disseminated mycobacterium infection indicates activity of systemic disease. Thus, even if the patient is not immunocompromised, an underlying systemic involvement should be ruled out.

Analysis of Inherited Optic Neuropathies.

BACKGROUND: Inherited optic neuropathies (IONs) cover a spectrum of clinically and genetically heterogenic conditions. Genetic evaluation of patients with IONs may enable their better clinico-diagnostic assessment and management of the disease. The aim of the present study was to determine the genetic condition related to the phenotype in patients with diverse inherited optic neuropathies. PATIENTS AND METHODS: A retrospective study was performed in 12 adults and 8 children of 8 non-related families. Clinical phenotyping, supported by color fundus, FAF, and OCT imaging, was performed. Genetic testing was obtained for all family members suspected for ION. RESULTS: Identification of pathogenic mutations in eight non-related families helped to confirm the diagnosis of ION. Affected from ION were ten patients (eight adults and two children; four women and six men). Bilateral Leber's hereditary optic neuropathy (LHON) was linked to the m.11778G>A mutation in two families (two affected and five carriers). Secondary homoplasmic LHON mutations in MT-ND1 (m.4216T>C) and MT-CO3 genes (m.9804G>A) were confirmed in two families (each one subject, three eyes affected), without detection of a primary LHON mutation. One member presented a picture of right-sited optic neuropathy associated with a c.220C>G mutation in the ACO2 gene and a heterozygous c.185C>T mutation in the LDLR gene. Autosomal dominant optic atrophy was confirmed in three non-related families (five subjects with bilateral ION), where molecular genetic analyses confirmed four different heterozygous mutations in OPA1: c.1847+1G>T; c.2497-1G>A, 297A>G and c.(2983+1_2984-1)_(c.*3211) (2 splicing mutations, 1 missense mutation, and 1 gross deletion encompassing exons 30 and 31). CONCLUSIONS: Combining clinics and molecular genetics when evaluating patients with IONs helps in characterizing disease and, therefore, is strongly recommended for such patients.