bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of tear film Osmolarity in glaucomatous and ocular hypertensive patients under topical therapies: A real life experience of a glaucoma unit
Authors: Rolle Teresa , Ghilardi Andrea , Malinverni Lorenza , Tibaldi Tommaso , Reibaldi Michele
Published: December 2022

Purpose: The aim of the study was to evaluate the presence of alterations in the tear film osmolarity and in other parameters that can define the OSD in POAG/OH patients treated with different topical therapies in order to better define the role of osmolarimetry in the clinical management of patients in a real life setting.

Methods: This is a cross‐sectional, observational study. All patients with POAG/OH treated with topical medications and 20 subjects age and sex matched as a control group, were consecutively and prospectively enrolled. The following exams were performed: tear film osmolarity assessed using Tearlab®, tear break‐up time (TBUT), corneal staining score (Oxford scale), ocular symptom assessment using Ocular Surface Disease Index (OSDI) questionnaire. These data were compared between POAG/OH patients and control group and correlations were analysed between tear film osmolarity and other DED parameters.

Results: 50 POAG/OH patients (25 M/25F; mean age 69 ± 17y) and 20 controls, matched for age and sex, were enrolled. The mean treatment duration was 2.5 ± 1.2 years. Benzalkonium chloride (BAK) was used in 92% of cases. The mean osmolarity value (mOsms/L) in POAG/OH patients was 306 ± 12 versus 296 ± 12 in control group (p < 0.05). TBUT (sec) was 5 ± 2 versus 9 ± 2 (p < 0.05). OSDI ranged from 0 to 96 and the mean value was 18 ± 19 in the study group vs 16 ± 14 in controls (NS). No significant difference was found in corneal staining between the two groups. In POAG/OH eyes tear film osmolarity values were ≤308 in 17/50 (34%) patients and in control group were 4/20 (20%). TBUT<8 s in 41/50(82%) vs 5/20 (25%). OSDI was <12 in 50% of cases vs 55% of controls, ranging from 13 to 32 in 36% versus 30% and from 33 to 100 in 14% versus 20%; corneal staining >1 in 12% versus 10%. Tear osmolarity was significantly correlated to TBUT (r = 0.11; p = 0.05).

Conclusions: The differences between OSM and TBUT are statistically significant between the two groups. OSDI score difference is not significant, but the self‐administered questionnaire has inherent limitations. Tear film osmolarimetry has the advantage of providing a quantitative, operator‐independent indication of possible ocular surface dysfunction and it may be useful in the real life practice of a glaucoma unit in identifying the most vulnerable patients who might benefit from a switch to BAK‐free preparations.
Tomography features of the lamina cribrosa and its scleral canal in different types and stages of the diabetic optic neuropathy
Authors: Karliychuk Maryna , Pinchuk Serhii , Bezditko Pavel
Published: December 2022

Lamina cribrosa morphology is ever changing in health and disease, and its changes might cause primary optic nerve damage and secondary damage due to decreasing of blood supplying and axoplasmic transport. Anatomical narrowing of the lamina cribrosa scleral canal may be a precondition of optic nerve and retina damage in diabetes mellitus (DM).

Purpose: to define the tomography changes of lamina cribrosa (LC) and its scleral canal depending on type and stage of diabetic optic neuropathy (DON).

Methods: 575 patients (1150 eyes) with type 2 DM and 50 non‐diabetic control persons (100 eyes) aged 55.9 ± 7.8 years were examined. LC thickness was measured with optical coherent tomography (OCT) using LC_Thickness_programm.m and main_low_noise_filters_programm.m. The area of LC scleral canal was measured with SD OCT using the LC_cut_position_programm.m and LC_diameter_calculation_programm.m.

Results: A correlation between type and stage of DON and LC thickness in diabetic patients was found. An average index of LC thickness in diabetic patients without DON was 1.4 times higher than in controls; in subclinical stage of axial DON – 1.9 times higher, in initial stage – 2.1 times higher, in severe stage of axial DON and diabetic papillopathy – 2.6 times higher, in anterior ischemic DON – 2.7 times higher, in dystrophic stage – 3.1 times higher than in controls (303 ± 56 μm) (р < 0.001). Scleral canal area in diabetic papillopathy was 35% less and in anterior ischemic DON was 21.6% less than that in controls. A direct correlation between the area of LC scleral canal and the state of optic nerve head was found in diabetic papillopathy and ischemic DON (r = 0.89, р < 0.001 and r = 0.93, р < 0.001 соrrespondingly).

Conclusions: A direct correlation between type and stage of DON and scleral LC thickness in patients with DM was revealed. Narrowing of LC scleral canal and thickening of LC were found to change in diabetic papillopathy and ischemic DON.
Neuronal and synaptic connectivity impairment along with the vascular alterations in the macula of diabetic patients
Authors: Albertos‐Arranz Henar , Ortuno‐Lizaran Isabel , Saez Xavier Sanchez , Pastor María José Ruiz , Martínez‐Gil Natalia , Lax Pedro , Cuenca Nicolas
Published: December 2022

Purpose: Retinal neurodegeneration in diabetic patients appears to occur along with the vascular abnormalities. Some structural and functional changes have been described in the retina of these patients. The aim was to describe the morphological alterations present in the retinal cells and the vascular network in the macula of human donor with diabetes.

Methods: Retinas of human donor with diabetes or diabetic retinopathy (n = 5) and control (n = 3) were processed in cross‐sections or flat mount retinas. The vascular network and the retinal cells were analysed in the macula through immunohistochemistry and confocal microscopy. Analysis of the vessel density was performed with the Angio‐tool software.

Results: Diabetic and control group had a mean age of 60 ± 10 and 62 ± 2 years, respectively. Capillary bends, vascular loops, microaneurysms and an increase of the vascular density were the main findings in the intermediate and deep capillary plexuses of the diabetic group. Disruption of the basement membrane of the retinal vessels and tractions due to the epiretinal membrane were observed in the superficial vessels. Interpericyte tunnelling nanotubes appeared altered in the plexuses of the diabetic retinas. Endothelial cell marker was accumulated inside the microaneurysms, and microglial nodules were surrounding them. Disruption of the external limiting membrane and swelling of Müller cells were present. Disorganization or loss of the outer plexiform layer observed with bassoon, vesicular glutamate transporter and synaptophysin as well as sprouting of the horizontal cells existed in some diabetic retinas. Cone photoreceptors seem to extend their axons to maintain the synaptic connectivity in the intraretinal cysts. Synaptic terminals of the bipolar cells in the plexiform layers were altered.

Conclusions: In addition to the specific vascular changes, alterations in the synaptic connectivity and the morphology of retinal cells are present in the fovea of diabetic patients.
Fluocinolone acetonide intravitreal implant for the treatment of macular edema: Long‐term outcomes from a single tertiary hospital
Authors: Gallén Leyre Sanz , Del Rio Noemi Ruiz , Vilaplana‐Mora J. M. , Alarcón‐Correcher F. , Natividad Sonia Andreu , Ibor F. García , Duch‐Samper Antonio M.
Published: December 2022

Purpose: Injectable long‐acting implant of Fluocinolone Acetonide (FAc) has proven useful for the treatment of macular edema of different etiologies. The aim of our study was to assess the real‐life safety and efficacy of FAc 0.19 mg intravitreal implant for the treatment of macular edema.

Methods: We retrospectively collected data from all patients with macular edema prescribed with FAc intravitreal implant between January 2019 and May 2022 in a single tertiary hospital. Central retinal thickness (CRT), visual acuity (VA), intraocular pressure (IOP) and need for cataract surgery were measured as the endpoints of interest at baseline and were reevaluated every 3 months.

Results: Finally, 41 patients, contributing 51 eyes, were included in the analysis. Most frequent indication for prescription was macular diabetic edema (n = 33, 64.7%), followed by uveitis (n = 9, 17.6%) and others (iris‐supported phakic intraocular lens, retinal vein occlusion, Irvinne Gass syndrome and post‐retinal detachment surgery; n = 9, 17.6%). In terms of efficacy, at a median follow‐up of 20.3 months, a reduction in CRT was observed (from 438 μm to 299 μmat at 12 months) and this resulted in an improvement in VA (from 0,30 to 0,41 at 12 months), mostly in uveitis group. In terms of safety and secondary effects, no endophthalmitis was reported and IOP increased at follow‐up with 20 eyes requiring topical IOP‐lowering drops. All phakic eyes at baseline (n = 10, 19.6%) were referred to cataract surgery in the follow‐up, at a mean of 13 months after FAc injection.

Conclusions: FAc intravitreal implant for the treatment of macular edema in real‐life patients resulted in improvement of both CRT and VA with predictable secondary effects and no major safety concerns.
Vitreo‐retinal injuries in the practice of padel, a problem on the rise
Authors: Merino Andrés Biescas , Merino Jacobo Yañez , Hermosín Mario Garcia , Rufas Inés Munuera , Navarro Damián García
Published: December 2022

Purpose: Paddle tennis is considered a sport with high ocular risk. The most frequent eye injuries are caused by the impact of shovels, balls or earth particles, with injuries to the posterior pole of the eye (retina and vitreous) being the most serious and can lead to loss of vision due to retinal detachment, choroidal tears or eye burst many times due to not using adequate protection. In this paper, we analyse posterior pole injuries and their treatment.

Methods: The cases of ocular injuries in the practice of paddle tennis in the last three years seen in the ophthalmology emergency service of our hospital have been collected.

Results: 34 patients have been included, 30 men and 4 women, with a mean age of 34 years. The initial visual acuity was 0.74 and the final visual acuity was 0.9. The lesions seen have been retinal edema, vitreous haemorrhages, retinal haemorrhages, retinochoroidal tears, retinal tears, macular hole, vitreous base avulsion and angular recession glaucoma, in many cases associating more than one type of injury. In most cases, topical treatment (25 cases), topical and oral (5 cases), laser (5 cases) and surgery (3 cases) have been performed. In no case, did they use eye protection.

Conclusions: Most of the cases presented good initial visual acuity, however, all presented potentially serious lesions in the posterior pole (retina and/or choroid), including two cases of retinal detachment and one angular recession glaucoma that required surgery. For this reason, it is necessary to insist on the use of approved polycarbonate protective glasses for all players and in case of ocular contusion, review by the ophthalmology service to assess the eye fundus regardless of the initial vision.
Optic nerve sheath diameter changes at altitude
Authors: Simpkins Ciaran , Westwood Jessica , Mayhook‐Walker India , Darby‐Smith Andrew , Normando Eduardo Maria , Morris Daniel
Published: December 2022

Purpose: This study aimed to assess variations in Optic Nerve Sheath Diameter (ONSD) as a correlate of Intracranial Pressure (ICP) during ascent to high‐altitude and to explore the relationship between ONSD and Acute Mountain Sickness (AMS). AMS is a high‐altitude illness characterized by headaches, lethargy, nausea and vomiting. At present there is no consensus on the pathophysiology of AMS. There are similarities in symptomology between AMS and raised ICP. A greater understanding of ICP at altitude and its role in AMS may yield new strategies for management of the illness.

Methods: We conducted a longitudinal cohort study involving 10 mountaineers climbing Mt Toubkal (4167 m). Participants underwent daily binocular ultrasound B‐scans at interval altitudes during the ascent. Altitude, AMS diagnosis and severity (using Lake Louise Score [LLS]) were recorded concurrently with ultrasound examinations. Ultrasound scans were reviewed by a blinded observer who measured ONSD and assessed image quality (1 = poor, 2 = moderate, 3 = good).

Results: During the ascent to 4167 m and return to low‐land, there was no significant variation in left (p = 0.97), right (p = 0.68) or mean (p = 0.86) ONSD. The ratio of ONSD to baseline was significantly (p = 0.038) greater in participants with AMS on Day 5; this was not consistent across all time points. No significant correlation between the ratio of ONSD to baseline and LLS was observed at any time point. Mean image quality was 2.12 (SD ± 0.65); images largely scored in the ‘Moderate’ – ‘Good’ range.

Conclusions: This study is reflective of changes in ONSD during slow ascent profiles commonly used in mountaineering. This suggests that ONSD and therefore ICP does not significantly vary during this style of ascent to 4167 m. We did not identify any convincing relationship between AMS and ONSD, adding to previous research suggesting the same. Considering the limitations of this study, it cannot stand alone to disapprove a causal relationship between ONSD and AMS.
Fundus autofluorescence pattern in different cases of cone inherited macular dystrophies
Authors: Boned‐Murillo Ana , Diaz Maria Dolores , Bartolome Isabel , Hospital Elvira Orduna , Gavas Javier Mateo , Fernández‐Espinosa Guisela , Pinilla Maria Sopeña , Lozano Isabel Pinilla
Published: December 2022

Purpose: To study fundus autofluorescence (FAF) with blue light excitation (488 nm) in different cases of cone inherited macular dystrophies an to assess differential characteristics.

Methods: We studied different cone inherited retinal dystrophies due primary to ABCA4 mutation with blue FAF and correlate the findings with the clinical impairment. We compared with the findings in other mutations.

Results: We presented 9 cases of Stargardt diseases with ABCA4 mutation with different blue FAF characteristics, from single macular impairment with an hypofluorescence, pattern, hyperreflective flecks around the central lesion or flecks extended outside the vascular branches. The extension of the flecks was no correlate with the degree of functional impairment. We compared with other cone dystrophies such as CRX mutation, with similar findings than the ones with only central impairment. Asymptomatic CRX mutation showed a hyperreflective central lesion.

Conclusions: FAF is an essential tool to diagnose and follow‐up inherited retinal dystrophies with primary macular manifestation. Same mutation and clinical stage could present different patterns.
Tear film stability in dry eye syndrome: Time and break‐up patterns
Authors: Gallo Vanessa , D'Ancona Fabrizio , Panzeri Alessia , Nucci Paolo , Villani Edoardo
Published: December 2022

Purpose: Comparison between traditional invasive methodologies and modern non‐invasive high‐tech methodologies for qualitative and quantitative evaluation in 3 groups of patients with dry eye disease.

Methods: Cross sectional study of 111 participants recruited consecutively at the eye clinic of San Giuseppe Hospital in Milan in 3 groups: healthy (n = 30), aqueous deficient dry eye ADDE) (n = 32) and evaporative dry eye (EDE) (n = 49) underwent osmolarity assessment, OSDI questionnaire, tear meniscus height measurement (TMH), Non‐invasive (NIKBUT‐first and NIKBUT‐average) and invasive (FBUT with fluorescein) tear film break up time, Meiboscore, corneal staining and Schirmer test.

Results: FBUT, Schirmer test, f‐NIKBUT and a‐NIKBUT were significantly different between the three groups (p < 0.001). FBUT and also f‐NIKBUT were lower in EDE group (4.46 ± 2.24) than other groups; In healthy and ADDE subjects, tear film break‐up time was located in the lower sector between the periphery average and the extreme. NiKBUT pattern was significantly different between the upper and lower peripheral, nasal and temporal periphery and the central temporal into the different groups (p < 0.05). Correlation analysis showed an inverse association between age and f‐NIKBUT (r = −0.358) between all patients. Corneal staining was more severe in ADDE patients.

Conclusions: In ADDE group the f‐NIKBUT was higher, almost at normal values, compared to FBUT. In a previous study, NIKBUT was found to be higher than FBUT due to non‐installation of dyes in the eye. In healthy and EDE subjects the tear film rupture was located in the lower sector between the average periphery and the extreme, probably due to a longer exposure time than in other areas. In EDE subjects, however, f‐NIKBUT was found in the central temporal and nasal sectors in according with previous studies. Average and f‐NIKBUT were negatively related with the age and also positively related to each other. FBUT and f‐NIKBUT were related to each other differently in 3 groups of patients; they could study different aspects of the same phenomenon, further studies are ongoing.

References

1. Mark D.P. Willcox, Pablo Argüeso, TFOS DEWS II Tear Film Report, Ocular Surface, 2017.

2. Michae L.A. Lemp, The Definition and Classification of Dry Eye Disease, 2007.
Evidence for visual cortical plasticity in retinitis Pigmentosa
Authors: Castelo‐Branco Miguel , Sampaio Joana , Silva Eduardo , Ferreira Sónia , Almeida Otilia C. d'
Published: December 2022

Purpose: Neural plasticity upon visual loss remains a very controversial phenomenon. We asked how the changes in peripheral visual input in adult Retinitis Pigmentosa patients would impact the stability versus plasticity of neuronal population receptive fields in early visual areas.

Methods: A total of 37 participants were recruited. The Retinitis Pigmentosa group (RP) included 12 patients with RP. The full‐field Control group (FFCnt) included 13 healthy participants that performed the original protocol (as the RP group); and an artificial scotoma Control group (ASCnt) (n = 12). Population Receptive Field (pRF) fMRI paradigms were used at 3 Tesla. The maximum field of view was 23° × 30°. The stimuli used for pRF estimation consisted in conventional single, 45° counter‐clockwise rotating wedge and expanding ring stimuli with a high‐contrast (~100%) flickering (8 Hz) checkerboard pattern. To resolve chronic from acute adaptive effects we performed an artificial scotoma experiment, in an independent control group.

Results: The general increase of pRF size on eccentricity was found in both Retinitis Pigmentosa and control individuals as expected. Interestingly, in RP, the regression slopes of pRF size and eccentricity in V1 and V2 seem to collapse in RP patients, in contrast with controls. Analysis of the regression lines adjusted to the mean pRF size along eccentricity in the calcarine sulcus of RP and matched ASCnt showed a significant difference between slopes (F(1,296) = 15.01, p < 0.001), corresponding to a group difference in pRFs size in more peripheral locations, suggesting plasticity. Artificial scotoma pRF mapping showed no evidence for rapid adaptation.

Conclusions: We found evidence for long term visual plasticity in adult Retinitis Pigmentosa patients as demonstrated by increased size of peripheral neuronal population receptive fields in early visual areas, which could be explained by rapid adaptation mechanism.
Neuropathic corneal pain impacts patient's quality‐of‐life dimensions more than dry eye disease
Authors: Mirzaee Leyla , Meka Akhil , Lopez Maria , Jamali Arsia , Dieckmann Gabriela , Koseoglu Dilruba , Ramesh Navneet , Khasksari Bijan , Cox Stephanie , Hamrah Pedram
Published: December 2022

Purpose: To compare the perception of ocular pain in patients with neuropathic corneal pain (NCP) and dry eye disease (DED), and to measure its impact on quality‐of‐life (QoL) dimensions (physical, psychological, social).

Methods: A retrospective, cross‐sectional study, comparative study was conducted, including NCP (N = 119) and DED (N = 43) patients. Demographic features, ocular pain assessment survey (OPAS), and ocular surface disease index (OSDI) scores were reviewed. The OPAS comprises physical (vision‐related), social and psychological dimensions of QoL through six items.

Results: The mean age of DED and NCP were 56.3 ± 15.7 and 56.2 ± 16.0 years, respectively (p = 0.966). The mean pain intensity scores (scale 0–10) in the last 24 h and 2 weeks were 2.04 ± 2.68 in DED patients and 5.03 ± 3.22 in NCP (p < 0.01) and 2.08 ± 2.91 (DED) and 4.77 ± 3.51 (NCP; p < 0.01) respectively. The interference of pain on QoL for DED and NCP patients was: reading/computer (DED 3.33 ± 3.24, NCP 5.54 ± 3.46, p = 0.003), driving/TV (DED 3.08 ± 3.28, NCP 4.59 ± 3.32, p = 0.024) for physical (visual related) dimension and Gen Act (DED 2.04 ± 2.77, NCP 3.87 ± 3.04, p = 0.001); Mood (DED 3.04 ± 3.39, NCP 5.66 ± 3.48 p = 0.001); Sleep (DED 2.32 ± 3.28, NCP 3.46 ± 3.18, p = 0.014) for the psychological dimension; enjoying life/social relations (DED 2.80 ± 3.26, NCP 5.15 ± 3.50, p = 0.001) for the social dimension of QoL. While pain had no significant impact on the visual dimension of QoL in DED (R = 0.14; p = 0.25), it had a significant impact in NCP patients (R = 0.41; p = 0.001). No significant difference in gender was resulting in any QoL dimension (p > 0.05).

Conclusion: Pain in patients with NCP has a more pronounced interference with physical, psychological, and social dimensions of QoL as compared to patients with DED. The vision‐related dimension of QoL is impacted by pain in NCP, but not in DED.
Spontaneous resolution of treatment‐resistant foveal capillary macroaneurysms in retinal diseases
Authors: Braham Imene Zhioua
Published: December 2022

Purpose: Capillary macroaneurysms (CMAs), may be observed in many retinal diseases causing chronic macular edema. A targeted photocoagulation can be efficient to close extrafoveal CMAs. However, treatment of foveal CMAs can be challenging. We report 2 cases of foveal CMAs with chronic edema resistant to intravitreal injections (IVI), which spontaneously resolved after discontinuation of treatment.

Methods: Patients with foveal aneurysms greater than 150 μm in diameter, related to retinal diseases and treatment‐resistant were evaluated with ophthalmologic examination and multimodal imaging.

Results: Case 1: a 74‐year old female with retinal branch vein occlusion complicated with chronic macular edema was referred for treatment. Foveal macroaneurysm was detected on indocyanine green angiography (ICGA) and was resistant to ranibizumab followed by aflibercept monthly IVI. Six months after stopping treatment, macular edema spontaneously resolved with occlusion of the CMA.

Case 2: a 82‐year old patient was treated for a chronic diabetic macular edema on his left eye. He received regular IVI of ranibizumab, aflibercept and dexamethasone implant without improvement. A retrofoveal CMA was noted on ICGA. After 4 months without IVI, the central macular thickness and the vision improved spontaneously.

Conclusions: Chronic macular edema related to foveal CMAs is usually resistant to anti‐VEGF and steroid intravitreal injections. In some cases, spontaneous resolution of the macroaneurysm can occur when treatment is stopped.
Efficacy and safety of pneumatic vitreolysis for management of vitreomacular traction syndrome
Authors: Braham Imene Zhioua
Published: December 2022

Purpose: To evaluate the outcome of small volume injection of perfluoropropane (C3F8) gas for symptomatic vitreomacular traction (VMT).

Methods: A retrospective review of eyes with VMT treated with a limited volume of 0.2 ml of C3F8 gas was performed with limited face‐down position. Main outcome measures were release of VMT, best‐corrected visual acuity (BCVA), central macular thickness (CMT) and adverse events.

Results: Ten consecutive patients with symptomatic VMT underwent pneumatic vitreolysis. Overall success was of 90% in VMT release. The CMT decreased from 397,8 μm ±) 81.87) preoperatively to 309,8 μm ±) 51.76) postoperatively (p < 0.001). Mean BCVA improved from 0.42 ±) 0.24) to 0.24±) 0.23) logMAR at 6 months (p < 0.001). One patient with a large VMT had no change in the optical coherence tomography aspect. Another patient with large VMT associated to large retrofoveal cyst has VMT release but formed a macular hole after gas injection. No other adverse events were seen.

Conclusions: Pneumatic vitreolysis with small volume of C3F8 and limited face‐down position is a viable option for treating VMT with few adverse events. Macular hole formation can occur in cases of large retrofoveal cysts.
Trends in glaucoma: Update on clinical trials and new targets to treat glaucoma
Authors: Kolko Miriam
Published: December 2022

Clinical trials with glaucoma have increased significantly over the last 30 years. The three main areas of clinical trials are in diagnostic tools, medical treatments, and new surgical strategies. While medical treatments have been the most common clinical trials, the number of clinical trials in surgery is now leading. In medical care, most new goals are new IOP‐lowering strategies, whereas clinical trials of neuroprotection and vascular modalities are still sparse. In addition to traditional medicine, dietary supplements and growth factors are also assessed for a potential anti‐glaucomatous effect. Within medical targets, the success rates for Phases II and III are below the reported success rate for all diseases and ophthalmology in general. The reasons for the low success rates can be explained, among other things, by the need for a stricter phenotyping of patients. Here, an overview of trends in clinical trials will be given and a future perspective will be discussed.
Retinal involvement in mitochondrial disease
Authors: Votruba Marcela
Published: December 2022

Retinal involvement in mitochondrial disease is a variable feature of mitochondrial dysfunction. The retinal pigment epithelium and photoreceptor layers can both be affected. It manifests with signs ranging from asymptomatic peripheral salt‐and‐pepper retinopathy to classic bone‐spicule pigmentary changes. The consequences can be progressive mild or severe visual field constriction and central visual acuity loss. The pathophysiological mechanisms involved in retinal dysfunction in mitochondrial disease are still being elucidated and may include a range of metabolic and bioenergetic defects.

Mitochondrial conditions affecting the eye that display prominent outer retinal involvement include.

(a) mitochondrial encephalomyopathy, lactic acidosis and stroke‐like episodes (MELAS) secondary to the m.3243A > G mtDNA mutation in MT‐TL1,

(b) neuropathy, ataxia and retinitis pigmentosa (NARP) secondary to the m.8993 T > G mtDNA mutation in MT‐ATP6,

(c) chronic progressive external ophthalmoplegia (CPEO), in particular the Kearns‐Sayre syndrome (KSS) secondary to single large‐scale mtDNA deletions, and.

(d) some newer entities, such as optic neuropathy and pigmentary retinopathy seen in patients with mutations in the gene SSBP1.

The features and diagnostic pathway for these conditions will be illustrated and discussed.
Keypoints in clinical presentations, lab tests and treatment options
Authors: James Teifi
Published: December 2022

Teifi James will explain the crucial importance of the history in the clinical presentation of Uveitis. He will discuss key signs and how to confirm their presence or absence. Teifi will also explain how the urgency of the situation depends on the clinical presentation. He will then proceed to consider which laboratory tests are appropriate depending on clinical presentation. He will close by mentioning the different treatment options that are available for Uveitis.
How to perform gonioscopy and normal findings in the angle
Authors: Schmidl Doreen
Published: December 2022

Although new techniques for the assessment of the anterior chamber angle have become available recently, gonioscopy remains the gold standard. Different lenses that can be used for gonioscopy and their application will be discussed. Further, suggestions for a systematic assessment of the anterior chamber angle will be presented. Normal findings in healthy eyes will be summarized.
Distinguishing infectious endophthalmitis from noninfectious inflammation – Cataract surgery and intravitreal injection
Authors: Ascaso Francisco Javier
Published: December 2022

With both cataract surgery and intravitreal injections, there is a risk of infectious or non‐infectious intraocular inflammation. The ability to differentiate between the two types of inflammatory reaction is important as the delay in treatment in the former case or unnecessary treatment in the latter case can have consequences.

Infectious endophthalmitis is usually associated with pain, hypopyon, severe anterior chamber reaction, hyperemia and significant vision loss, while symptoms associated with sterile endophthalmitis are often less severe. Nevertheless, although rarely, non‐infectious intraocular inflammation can be potentially vision‐threatening after phacoemulsification cataract surgery or intravitreal injection. Since it may be easily mistaken for infectious endophthalmitis, a clear understanding of this pathology is essential. If the ophthalmologist is not sure about the sterile origin of the inflammation, this complication must be treated as an acute endophthalmitis because of the severe visual outcome of this intraocular infection without antibiotic therapy. The aetiology of sterile endophthalmitis remains uncertain and a multifactorial origin must be considered. We will provide further insight into the mechanisms, causative factors and clinical differences among various types of inflammation, with the goal that clinicians can reduce the risk of these events in the future.
Can we measure neuroprotection yet in glaucoma?
Authors: Normando Eduardo
Published: December 2022

Glaucoma is a neurodegenerative disease characterized by axonal injury and loss of retinal ganglion cells (RGCs). Several neuroprotective compounds have been explored in preclinical studies and some of them have progressed to clinical trials in glaucoma. To date, these clinical trials have produced inconclusive results manly due to the lack of effective metrics able to quantify neuroprotection.

Here we will explore the most recent advances in measuring neuroprotection in Glaucoma.
Development of neuroprotective agents – Possible endpoints and regulatory considerations
Authors: Garhöfer Gerhard
Published: December 2022

Neuroprotection, the therapeutic approach aiming to prevent neuronal degeneration and loss of function, is a promising and fast developing field to treat various systemic and ocular degenerative diseases, including Alzheimer's disease, Parkinson's disease and glaucoma. As for the eye, despite may efforts, there is currently no approved neuroprotective agent available. This talk will summarize the current challenges in the development of ocular neuroprotective agents. Possible clinical endpoints will be covered and regulatory requirements will be discussed.
Sigma − 1 receptor activation as a new option for the treatment of glaucoma in preclinical models
Authors: Fekete Andrea , Tran Minh N. , Besztercei Balazs , Torok Gyorgy , Medveczki Timea , Takácsi‐Nagy Anna , Gasull Xavier , Szabo Attila J. , Kovacs Illes , Hodrea Judit
Published: December 2022

Introduction: Trabecular meshwork (TM) is the main pathway for aqueous humour drainage. The fibrotic‐like remodelling of the actin cytoskeleton in TM cells results in accumulation of extracellular matrix proteins leading to altered stiffness and impaired outflow. These are the primary cause of increased intraocular pressure (IOP) and glaucoma. Our group owns a world‐wide patent for various Sigma‐1 receptor (S1R) agonists as novel antifibrotic compounds. Fluvoxamine (FLU), a potent S1R agonist, decreases the levels of key elements of fibrosis in the kidney and in the lung, and preserves organ function.

Aim: Here in vitro (1) we identified the presence and localization of S1R in the eye, (2) studied S1R activation on cytoskeletal rearrangement and (3) investigated the IOP lowering‐effect of FLU in the in vivo mice‐model of glaucoma.

Methods: S1R was detected on HTM5 and on primary MsTM cells. Cells were treated platelet‐derived growth factor (PDGF, 24 h, 20 ng/ml) combined with 10 μM of FLU. Cell proliferation and migration were measured band F‐actin formation was visualized by phalloidin staining. To induce IOP C57BL/6J mice were weekly injected (n = 8–12/group) with vehicle or Dexamethasone Acetate (Dex) through periocular conjunctival fornix to both eyes. FLU eye drops (30 mM) were given bilaterally twice daily after 1 week of Dex. IOP was measured with Icare Tonolab weekly.

Results: S1R was present both in TM cells and is localized in the endoplasmic reticulum. PDGF‐induced cell proliferation, migration and cytoskeletal rearrangement were ameliorated or even prevented by FLU treatment. Dex increased the IOP in WT mice after 3 weeks from baseline 17.26 ± 1.46 to 18.61 ± 1.05 mmHg (+7.82%; p < 0.05). Two‐week treatment of FLU‐containing eye drop was not harmful to the eyes and lowered IOP to 16.90 ± 1.19 mmHg (−9.18%; p < 0.05) compared to Dex group.

Conclusions: FLU is non‐toxic and reduces profibrotic factor‐induced cytoskeletal rearrangement and cell proliferation of TM cells. FLU treatment effectively prevents the increase in IOP. Thus Sigma‐1 receptor agonists could be potential candidates for the development of a novel drug candidate for glaucoma.

Grants: OTKA‐ K135398, LP2021‐3/2021, TKP2021‐EGA‐24.
Pioneer in refractive lens surgery
Authors: Grzybowski Andrzej
Published: December 2022

Wincenty Fukala (1847–1911) was born in a Polish family in Zolkiew in Polish Galicia (now Ukraine). He studied medicine in Vienna. He specialized in ophthalmology under the well‐respected professor, Karl Ferdinand von Arlt. He was a pioneer in systematically extracting the clear crystalline lens in young patients with high myopia (Fukala operation). This is the earliest refractive surgery performed in ophthalmology. He demonstrated the benefit to this group of increased visual acuity, which enabled them to work, and ophthalmologists gradually began to carry out surgery in high myopes worldwide. He persisted in operating despite the vigorous opposition of several authorities but, through sheer determination he convinced sceptics of the efficacy of his surgical method of lens dissection. He performed the first lens discission in 1887 and in 1894, he had successfully treated 44 patients. The late complication of retinal detachment, which was not understood until years later, eventually led surgeons to abandon the procedure until the recent improvements in both lenticular and retinal surgery techniques that led to better prognosis. He studied trachoma in Egypt in 1872. His research on scrofulous eye disease led him twice to the United States, in 1891 and 1892. Fukala also developed highly successful, pioneering techniques for the treatment of ectropion in blepharitis, of trachoma, and of shallow sockets following enucleation. In glaucoma, he recommended early iridectomy of the fellow eye when the first eye has gone blind. He was also an expert on the history of ancient European texts and of Arabic ophthalmology.
Autophagy in age‐related macular degeneration
Authors: Kaarniranta Kai
Published: December 2022

Age‐related macular degeneration (AMD) is the leading cause of visual impairment in the aging population with limited understanding of its pathogenesis and a lack of effective treatment. The progression of AMD is initially characterized by atrophic alterations in the retinal pigment epithelium, as well as the formation of lysosomal lipofuscin and extracellular drusen deposits. Cellular damage caused by chronic oxidative stress, protein aggregation and inflammatory processes may lead to geographic atrophy and/or choroidal neovascularization and fibrosis. The role of macroautophagy/autophagy in AMD pathology is steadily emerging. Selective and secretory autophagy and their role in drusen biogenesis, senescence‐associated secretory phenotype, inflammation and epithelial‐mesenchymal transition in the pathogenesis of AMD are discussed.
Bilateral changes in corneal sensitivity after unilateral corneal infections
Authors: Gallar Juana
Published: December 2022

Ocular infections such as herpes simplex virus (HSV) keratitis result in ocular sensitivity changes. During acute HSV episodes and eventually during postherpetic outbreaks, spontaneous pain and hyperalgesia are experienced, being reduced by treatment with Na+ channel blockers (not only by local anaesthetics but also by gabapentin, lacosamide or amitriptyline). At the same time, patients commonly develop hypoesthesia due to the decrease of sensitivity to mechanical stimulation, whose appearance could be due to the internalization of Na+ channels in trigeminal sensory neurons innervating the infected cornea.

When explored using a gas esthesiometer that allows selective mechanical, chemical, heat and cold stimulation, HSV‐infected corneas showed those sensitivity disturbances to be expected when corneal polymodal nociceptor activity is altered. On the contrary, sensitivity to cold stimuli is not modified, which suggest that cold thermosensitive ocular neurons are not infected by the virus. A surprising result is the alteration, in the same sense although to a lesser degree, of the sensitivity of the contralateral eye. This contralateral altered sensitivity could be caused by a subclinical HSV infection of the contralateral side. Another possibility is that to be due to a neuroimmune interaction that ends up affecting the activity of sensory nerves of both eyes, in a similar way to what happens in non‐infectious inflammatory processes affecting only one eye.

(PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103)
Monovision revitalized
Authors: Beiko George
Published: December 2022

Following cataract surgery in which the target refraction is emmetropia with a monofocal IOL, it has been found that 30–40% of patients achieve functional near vision as well. Further investigation of this outcome has determined that nature has optimized certain ocular parameters to allow this to occur. By understanding these factors, it is possible to plan our refractive outcome to provide similar outcomes for most of our surgical cataract cases. This planning involves measuring the preoperative pupil size and corneal spherical aberrations, using an intraocular lens that does not adjust spherical aberration, and targeting the refractive outcome based on these findings. This approach will be presented in the session.
Gene therapy of glaucoma: Just an attractive experimental approach?
Authors: Comes Núria
Published: December 2022

In recent years, much progress has been made in the identification of the genes involved in the physiology of glaucoma and the development of new gene‐based therapies. The eyeball has ideal characteristics for gene therapy due to its location and immunological properties. Gene delivery through viral and particle‐based vectors to target tissues makes gene therapy a more specific and effective treatment than existing conventional treatments. Experimental gene therapy strategies for glaucoma primarily targets trabecular meshwork (TM) (to decrease intraocular pressure) and retinal ganglion cells (for neuroprotection).

A chronic disease such as glaucoma, requires the use of vectors that allow long‐term gene expression with low toxicity and immune response. Some examples of experimental gene therapy for glaucoma are the efficient transduction of self‐complementary adeno‐associated viruses – metalloproteinase 1 (MMP1) into the TM in a steroid‐induced ocular hypertension model in sheep1. On the other hand, different studies have reported an increased survival of retinal ganglion cells after a single intravitreal injection of adenoviruses carrying brain‐derived neurotrophic factor (BDNF) in a rat model of glaucoma2.

To develop gene therapy at a therapeutic level it is necessary to broaden our knowledge of the expression and regulation mechanisms of candidate genes in order to control the efficiency and stability of their effect. The specificity of the vectors and the safety to prevent their spread to the rest of the organism must also be improved. Thus, it is necessary to continue devoting efforts to the development of safe and effective gene therapy for glaucoma.

References

1. Borrás T, Buie LK, Spiga MG. Gene Ther. 2016;23:438–49.

2. Ren R, Li Y, Liu Z, et al. Investig Ophthalmol Vis Sci. 2012;53:1003–11.
Large hole in macular surgery
Authors: Chichur Diana
Published: December 2022

Purpose: To evaluate the anatomical and functional results in eyes with large macular holes using inverted flower ILM flap technique.

Methods: This clinical study included 58 eyes with large macular holes, which were divided into 2 groups: first group included 36 eyes with idiopathic macular holes and second group – 22 eyes with myopic macular holes. In both groups diameter of the hole was more than 600 μm. All eyes were treated using an inverted flower flap technique, C3F8 gas tamponade and face‐down posturing. The hole closure, postoperative visual acuity and OCT data were analysed at 1 month and 6 month after the surgery.

Results: The inverted flower ILM technique was successful in 100% of the cases. We could observe significant postoperative improvements of visual acuity (p < 0.05) in all eyes. However, the first group showed better functional results compared to the second group. Complete resolution of ellipsoid zone defects was observed on 22 eyes (61.1%) in the first group and on 9 eyes (40.9%) in the myopic group.

Conclusion: The inverted flower flap technique confirmed its effectiveness for the closure of large macular holes and good recovery of photoreceptor layers and, consequently, functional result improvement.
Iatrogenic macular detachment for large macular holes: How to improve this technique
Authors: Lytvynchuk Lyubomyr
Published: December 2022

Iatrogenic macular detachment (IMD) with subretinal injection of balance salt solution (BSS) was proposed as an alternative treatment of the large, persistent and chronique macular holes (MH). Subretinal administration of BSS is aimed to detach the edges of the MH decreasing the stiffness and increasing the elasticity of the retina. Hence, the closure of the MH could be improved. Nevertheless, there are still cases that remain refractory to this approach. Preliminary observational studies of the surgery flow with the use of intraoperative optical coherent tomography revealed that in majority of cases after BSS was injected into subretinal space there was strong remaining almost circumferential adhesion between retinal pigment epithelium and photoreceptor outer segments at the edge of MH base. These data differ from the visually percepted MD and showed that in studied cases approximately just 5% to 20% of MH edge circumference were elevated predominantly in temporal area. Subretinal BSS blebs appeared to merge with each other within the macula but outside the MH edges. Additionally, there were no correlation between the size or height of the bleb with the extension of the MD at MH edges. It was noticed that nasally to the MH the adhesion between RPE and OPS was stronger. The causes of this adhesion remain unclear. This hypothesizes that separation of the adhesion could improve the closure rate of the refractory MH using IMD technique. Development of the new surgical approaches together with novel instruments to address the separation of the strong adhesion at the MH edge shall be considered in order to improve the results of iatrogenic macular detachment (IMD) technique in treatment of large, persistent and chronique MH.
Rock inhibitors and antisense oligonucleotides for Fuchs corneal endothelial dystrophy
Authors: Wylegala Adam
Published: December 2022

Fuchs corneal dystrophy (FECD) is the most common primary cause of corneal endothelial dystrophy. FECD is a complex disease where interaction between multiple genetic and environmental factors results in endothelial cells apoptosis and atypical extracellular matrix deposition. Due to the shortage of donor tissue, and high costs of transplants, a topical therapy for treating corneal endothelial dysfunction is urgently required. The topical treatment of several agents has been investigated as therapies for FECD, by the promotion of endothelial cell proliferation and migration, in experimental models of the disorder. ROCK1 and ROCK2 inhibition promotes cell adhesion, prevents apoptosis, and enhances the proliferation of and human corneal endothelial cells. These therapies have involved the knockdown of connexin by siRNA, the release of cell–cell contact inhibition with EDTA, and inhibition of Rho‐associated protein kinase (ROCK) with Y‐27632. Recently several papers showed that Ripasudil, a rho kinase inhibitor, has been shown to promote corneal endothelial wound healing in animal models and in clinical trials. An antisense oligonucleotide (ASO) has also been developed to target the repetitive RNA. This has been shown to decrease foci formation and reversal of misplacing in ex‐vivo FECD specimens. Antisense oligonucleotides (ASO) reduced the RNA aggregates and their toxic downstream events in patient cells. ASO has to be designed to target a particular genetic mutation. This new medical‐based regenerative therapy may provide a less invasive and more effective method for treating patients with FECD.
Targeting corneal dystrophies for genetic treatment; challenges and limitations
Authors: Balidis Miltos
Published: December 2022

The cornea is an ideal organ for gene therapy. Its immune‐privileged status, effortless accessibility for treatment with gene therapy agents and visual monitoring are significant aspects for gene therapy. Various viral and non‐viral vectors have been tested for delivering genes to the cornea. Viral vectors offer several fold higher transduction efficiencies and long‐term gene expression compared to non‐viral vectors.

Gene therapy is also an attractive approach for the treatment of ocular surface disorders such as corneal scarring and neovascularization. Over‐expression of vasoinhibin‐1 or decorin, can reduce corneal neovascularization.

Genetic engineering for corneal dystrophies treatment is at the very early stage. Potential treatments for FECD and TGFBI‐related corneal dystrophies may provide some therapeutic benefit.
Astrocyte activation and protein aggregation in the retina of Alzheimer's disease patients
Authors: Di Angelantonio Silvia , Pediconi Natalia , Mautone Lorenza , Pitea Martina , Grimaldi Alfonso
Published: December 2022

Alzheimer's disease (AD), a primary cause of dementia in the aging population, is characterized by intracellular and extracellular aggregates of misfolded proteins, as amyloid‐beta plaques and tau tangles, together with neurodegeneration and glial activation in the brain. It is commonly thought that the lack of early diagnostic criteria is among the main causes of pharmacological therapy and clinical trials failure; therefore, the actual challenge is to define new biomarkers and non‐invasive technologies to measure neuropathological changes in vivo at pre‐symptomatic stages. Recent evidences obtained from human samples and mouse models indicate the possibility to detect protein aggregates and other pathological features in the retina, paving the road for non‐invasive rapid detection of AD biomarkers. Here, we report the presence of amyloid beta plaques, tau tangles, neurodegeneration and detrimental astrocyte and microglia activation according to a disease associated microglia phenotype (DAM). Thus, we propose the human retina as a useful site for the detection of cellular and molecular changes associated with Alzheimer's disease.

We also developed novel 2D and 3D in vitro models of AD related retinal tauopathy, obtaining derived retinal cultures from iPSC harbouring an intronic tau mutation. We report here that mutated tau induces not only tau hyperphosphorylation, but also impaired retinogenesis and altered astrocytic development.