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).

Swiss Multicenter Ab Interno XEN45 Gel Stent Study: 2-Year Real-World Data.

INTRODUCTION: The aim of this study was to investigate the 2-year postoperative efficacy of the XEN45 Gel Stent by evaluating the reduction of intraocular pressure (IOP) and the need for eye pressure-lowering medications in a multicenter setting in Switzerland. METHODS: Patients with various types of glaucoma who received a XEN45 Gel Stent with or without combined phacoemulsification cataract surgery at five hospitals in Switzerland were retrospectively enrolled. Pre- and postoperative IOP, the number of antiglaucoma medications, and the need of subsequent interventions to control IOP were assessed. The success rate was defined as a ≥ 20% reduction of IOP 2 years postoperatively without the need for subsequent glaucoma surgery. RESULTS: A total of 345 eyes were included: 44.3% with primary open-angle, 42.0% pseudoexfoliation, and 13.7% with other types of glaucoma. Of these, 206 patients were followed for 2 years. Preoperatively, the mean IOP was 26.3 ± 8.9 mmHg and the mean number of antiglaucoma medications administered was 3.0 ± 1.3. Two years postoperatively, the success rate was 66.0% (95% confidence interval 59.3-72.1%), the IOP had dropped by 43.8% to 14.8 ± 5.7 mmHg, and the number of medications was reduced by a mean of 2.0 ± 1.7 per day. Postoperative complications and the need for interventions remained low. CONCLUSION: The XEN45 Gel Stent successfully reduced IOP and the number of antiglaucoma drugs in most patients at 2 years postoperatively.

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.

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.

The Presence of Hyperreflective Foci Reflects Vascular, Morphologic and Metabolic Alterations in Retinitis Pigmentosa.

BACKGROUND: The presence of hyperreflective foci (HRF) in retinitis pigmentosa (RP) is a potentially new finding. We investigated the presence of HRF in SD-OCT images in eyes with RP and its relation to vascular, morphologic and metabolic findings in RP. METHODS: The study was performed on 42 RP patients and 24 controls. Using SD-OCT, we calculated the amount of HRF within the entire retina (HRF-ER) and the outer nuclear layer (HRF-ONL). Retinal vessel diameters (µm) and oxygen saturation (%) values were measured using Oxymap T1. We evaluated the mean diameter in retinal arterioles (D-A) and venules (D-V), the corresponding oxygen saturation values (A-SO2, V-SO2) and the oxygen saturation difference (A-V SO2). RESULTS: RP differed from controls by HRF-ER, HRF-ON and EZ-length (p < 0.001). D-A and D-V were narrower and A-SO2 and V-SO2 were higher in RP (p ≤ 0.001). Within RP, significant interactions were found between the HRF-ER* group and: BCVA, EZ length, D-A, A-SO2 and A-V SO2 (p ≤ 0.018). The HRF-ONL* group interactions were significant for: BCVA, EZ length, D-A, A-SO2 and A-V SO2 (p ≤ 0.014). CONCLUSION: The present study highlights the presence of HRF to reflect the vascular, morphologic and metabolic alterations in RP. These biomarkers seem to be associated with remodeling and apoptosis that occur with the progression of degeneration.

Peripapillary Oxygenation and Retinal Vascular Responsiveness to Flicker Light in Primary Open Angle Glaucoma.

The aim of our study was to evaluate peripapillary oxygenation and its relationship to retinal vascular responsiveness to flicker light in patients with primary open angle glaucoma (POAG). Retinal vessel oxygen saturation was measured in 46 eyes of 34 Caucasian patients with POAG and in 21 eyes of 17 age-matched controls using the oximetry tool of Retinal Vessel Analyser (RVA: IMEDOS Systems UG, Jena, Germany). The mean oxygen saturation of the major arterioles (A-SO2; %) and venules (V-SO2; %), as well as the corresponding arterio−venular difference (A-V SO2; %), were calculated. We also measured retinal vascular responsiveness (RVR) to flicker light by means of RVA. Glaucoma patients were divided in two subgroups according to their median arteriolar and venular vascular responsiveness to flicker light (AFR and VFR). Glaucomatous damage was assessed by optical coherence tomography (Carl Zeiss Meditec, Dublin, CA, USA) and static automated perimetry (Octopus, program G2/standard strategy: Haag-Streit International, Köniz, Switzerland). In addition, we calculated the mean peripapillary oxygen exposure [ppO2E; %/µm] by dividing the mean A-V SO2 with the mean retinal nerve fibre layer (RNFL) thickness. In glaucoma patients, A-SO2 and V-SO2 values were significantly increased, and their difference decreased when compared to controls (p < 0.017; linear mixed-effects model). Grouped with respect to retinal vascular responsiveness to flicker light, subjects with reduced VFR (≤2.9%) had significantly higher ppO2E (0.49 ± 0.08%/µm, respectively, 0.43 ± 0.06%/µm; p = 0.027). Additionally, higher ppO2E in glaucoma patients correlated negatively with the neuroretinal rim area (p < 0.001) and the RNFL thickness (p = 0.017), and positively with the mean defect of the visual field (p = 0.012). Reduced venular vascular responsiveness in our glaucoma patients was associated with increased peripapillary oxygenation exposure. Thus, ganglion cells and their axons in glaucomatous eyes with reduced retinal vascular responsiveness are prone to be more exposed to higher oxidative stress, probably contributing to the further progression of glaucomatous damage.

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.

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.

Patients with central serous chorioretinopathy not only have pachychoroidal disorders but also altered retinal metabolic function.

PURPOSE: The aim of our study was to compare metabolic (oxygen saturation; %) and anatomical (diameter; µm) retinal vessel parameters of patients with central serous chorioretinopathy (CSC) to those of controls. METHODS: In this prospective cross-sectional cohort study, 72 eyes of patients with CSC were compared with 21 eyes of healthy controls. Of the 72 patients, 52 had chronic, nonactive CSC (subgroup nCSC) and 20 had active CSC (subgroup aCSC), according to activity on fluorescein angiography. Retinal vessel oximetry (RO) was performed using the Oxymap T1 oximeter. Oxygen saturation in all major peripapillary retinal arterioles (A-SO2 ) and venules (V-SO2 ) was measured, and their difference (A-V SO2 ) was calculated. In addition, we evaluated the corresponding diameter in retinal arterioles (D-A) and venules (D-V). For statistical evaluation, ANOVA-based linear mixed-effects models were calculated (SPSS®; p < 0.05). RESULTS: Central serous chorioretinopathy (CSC) patients had significantly higher A-SO2 and V-SO2 compared to that of controls (p = 0.031 and p = 0.018 respectively). Especially, the subgroup of aCSC patients showed significantly higher A-SO2 and V-SO2 values (p = 0.027 and p = 0.034, respectively). In addition, superotemporal and superonasal quadrant location showed significant interactions with A-SO2 and V-SO2 (p ≤ 0.03). Diameter in retinal arterioles (D-A), an venules (D-V) and A-V SO2 findings showed no significant differences (p > 0.096). CONCLUSION: These data indicate that patients with CSC have altered metabolic function. The presence of disease activity showed the greatest influence on RO measurement, both compared to controls and to those with inactive chronic CSC disease.

The artificial iris - Analysis of various implantation techniques after ocular trauma.

PURPOSE: The aim of this study is to analyze the outcome of various techniques for a custom-made iris prosthesis implantation as part of reconstructive anterior segment surgery following traumatic aniridia. METHODS: This retrospective interventional study was done for 6 eyes that received an artificial iris as secondary reconstructive measure for photophobia and unsatisfactory vision following initial globe repair. Different implantation techniques were employed. These included simple sulcus implantation, implantation of a composite (iris prosthesis with attached intraocular lens) implant, and combinations with phacoemulsification, vitrectomy, and penetrating keratoplasty. RESULTS: In all cases, the artificial iris was implanted successfully. In the follow-up period (1-48 months), postoperative complications included rhegmatogenous retinal detachment, prolonged intraocular inflammation, and corneal transplant decompensation due to graft rejection. There was no case of secondary glaucoma. Complications could be managed successfully. All patients showed improved best-corrected visual acuity and were satisfied with functional and cosmetic results. CONCLUSION: This case series highlights the different implantation techniques for reconstruction of the anterior segment after ocular trauma. The versatility of the custom-made iris implant accounts for a wide range of applications and the foldable material reduces the need for large incisions in the already traumatized eye.

Microvascular and metabolic alterations in retinitis pigmentosa and Stargardt disease.

PURPOSE: The aim of our study was to evaluate retinal microvascular changes recorded with optical coherence tomography angiography (OCTA) and the metabolic function measured with retinal oximetry (RO) in patients with retinitis pigmentosa (RP) and Stargardt disease (STGD). METHODS: In this prospective, noninterventional study, OCTA and RO were performed on 107 eyes (56 subjects): 53 eyes diagnosed with RP without the presence of macular oedema (no-ME-RP), 26 eyes with STGD, and 28 control eyes. Main outcome measures were the mean superficial (FAZ-S; mm2 ) and deep foveal avascular zone (FAZ-D; mm2 ) measured with OCTA as well as the mean arterial (A-SO2 ; %), venular (V-SO2 ; %) oxygen saturation, their difference (A-V SO2 ; %) and the corresponding mean diameters of the peripapillary retinal arterioles (D-A; µm) and venules (D-V; µm) determined with RO. RESULTS: Stargardt disease (STGD) patients differed from controls and no-ME-RP by an enlarged FAZ-S and reduced A-SO2 and V-SO2 (p ≤ 0.013). No-ME-RP eyes presented with attenuated vessels (p < 0.001) and increased A-SO2 and V-SO2 (p ≤ 0.012) compared to controls and STGD. The FAZ-D showed significant interactions with A-SO2 (p = 0.003) in no-ME-RP while the FAZ-S correlated with visual acuity in no-ME-RP (p = 0.007) and STGD (p = 0.034). CONCLUSION: Retinitis pigmentosa (RP) and Stargardt disease (STGD) patients suffer from microvascular and metabolic alterations, however, showing a different pattern. A combined microvascular-metabolic model may therefore allow to more precisely characterize RP and STGD as well as presumably other inherited retinal diseases.

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.

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.