bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between central corneal thickness and inter‐eye disease severity in primary angle closure glaucoma
Authors: Nongpiur Monisha , Umapathi Ruthra , Hliang Tin , Aung Tin
Published: January 2024

Aims/Purpose: To determine whether subjects with asymmetric primary angle closure glaucoma (PACG) demonstrate greater central corneal thickness (CCT) asymmetry compared to those with symmetrical disease severity.

Methods: The following clinical data were retrospectively extracted from the case records of 281 PACG subjects: presenting intraocular pressure (IOP), visual field mean deviation (MD) at presentation, CCT, anterior chamber depth (ACD), and axial length (AL). The eye with the worse visual field MD was considered the worse eye. Asymmetric PACG was defined as the inter‐eye visual field MD difference of greater than 5 dB; and symmetrical PACG disease as an inter‐eye difference of less than 5 dB. Subjects with previous acute primary angle closure were excluded.

Results: Based on the definitions, a total of 160 out of 281 PACG subjects (56.9%) presented with asymmetrical disease and 121 (43.1%) with symmetrical disease. Subjects with asymmetric disease had a significantly thinner CCT in the worse eye (529.2 ± 35.2 μm) compared to the fellow eye (535.3 ± 37.2 μm) (p < 0.001), and higher presenting IOP (28.8 ± 12.0 vs 20.1 ± 8.4 mmHg, p < 0.001), but no inter‐eye differences were observed for measurements of AL (p = 0.71) and ACD (p = 0.51) respectively. For patients with symmetric disease, no significant inter‐eye differences were observed for CCT (531.7 ± 31.2 vs 532.9 ± 32.4 μm, p = 0.38), AL (p = 0.30) and ACD (p = 0.31), but the worse eye had significantly higher IOP (22.7 ± 7.9 vs 20.6 ± 6.9 mmHg, p < 0.001). In the asymmetric disease group, 30.6% of subjects had a thinner CCT (≥ 10 μm) in the worse eye compared to 16% of subjects in the symmetric group. There was no correlation between inter‐eye CCT difference and inter‐eye difference of visual field MD (p = 0.17).

Conclusions: In PACG subjects with asymmetric disease at presentation, eyes with more severe disease have a thinner CCT and higher presenting IOP. Whether CCT is an independent risk factor for PACG through mechanisms beyond its influence on IOP measurements remains to be established.
Automated analysis of vessel morphometry in retinal images from a Danish high street optician setting
Authors: Freiberg Josefine , Welikala Roshan , Rovelt Jens , Owen Christopher , Rudnicka Alicja , Kolko Miriam , Barman Sarah
Published: January 2024

Aims/Purpose: To evaluate the test performance of the QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) software in detecting retinal features from retinal images captured by health care professionals in a Danish high street optician chain, compared with test performance from other large population studies (i.e., UK Biobank) where retinal images were captured by non‐experts.

Methods: The dataset FOREVERP (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability, Pilot) contains retinal images obtained from a Danish high street optician chain. The QUARTZ algorithm utilizes both image processing and machine learning methods to determine retinal image quality, vessel segmentation, vessel width, vessel classification (arterioles or venules), and optic disc localization. Outcomes were evaluated by metrics including sensitivity, specificity, and accuracy and compared to human expert ground truths.

Results: QUARTZ's performance was evaluated on a subset of 3682 images from the FOREVERP database. 80.55% of the FOREVERP images were labelled as being of adequate quality compared to 71.53% of UK Biobank images, with a vessel segmentation sensitivity of 74.64% and specificity of 98.41% (FOREVERP) compared with a sensitivity of 69.12% and specificity of 98.88% (UK Biobank). The mean (± standard deviation) vessel width of the ground truth was 16.21 (4.73) pixels compared to that predicted by QUARTZ of 17.01 (4.49) pixels, resulting in a difference of −0.8 (1.96) pixels. The differences were stable across a range of vessels. The detection rate for optic disc localisation was similar for the two datasets.

Conclusions: QUARTZ showed high performance when evaluated on the FOREVERP dataset, and demonstrated robustness across datasets, providing validity to direct comparisons and pooling of retinal feature measures across data sources.
Steroid induced glaucoma in the paediatric population
Authors: Mtalai Naoual , Ghizlane Daghouj , Hamdani Hind , Loubna Elmaaloum , Bouchra Allali , Asmaa Elkettani
Published: January 2024

Aims/Purpose: Steroid induced glaucoma is an iatrogenic pathology secondary to the prolonged use of corticosteroids, it is a serious pathology with a high risk of blindness. The aim of this study is to evaluate the epidemiological, clinical, therapeutic and evolutionary profile of steroid induced glaucoma in children.

Methods: It is a retrospective study of cases treated between November 2007 and February 2022, including patients followed in the paediatric ophthalmology department of Casablanca for steroid induced glaucoma.

Results: Our study involved́ 35 children (60 eyes), including 20 boys and 15 girls, with an average age of 12 years. The involvement was bilateral in 25 eyes. All the patients had a history of discontinuous self‐medication with local corticosteroids for a mean period of 5 years. The initial condition that led to the use of steroids was in 19 cases allergic conjunctivitis, in 10 cases it was used for recurrent meibomian cysts, 3 cases of uveitis, 2 cases of blepharitis and one episcleritis. 60% eyes had visual acuity raging between 0.1 to 0.3. Mean Intraocular pressure was 36 ± 1 2 mmHg. Mean vertical cup disc ratio was 0.68 ± 0.25. all our patients had an open angle on gonioscopy and severe perimetric deficits were noted in all our patients. 19 eyes (32%) had an associated cataract. IOP was controlled after the withdrawal of steroids in 8 eyes, associated to antiglaucoma treatment in 22 eyes. The surgical management consisted of a Trabeculectomy + IP + 5 F.U in 30 eyes. Cyclophotocoagulation was not required in any of the patients. On a follow up of 24 months, the average final visual acuity was <2/10th and the tonometric results were globally good with a stabilization of the papillary excavation and visual field in 82% of the cases.

Conclusions: Steroid induced glaucoma is a condition in which the functional prognosis is at risk, especially in young patients. It shows the importance of regular monitoring of the IOP in patients undergoing corticosteroid treatment. The first line of treatment consist of the prevention: awareness of the risks of self‐medication by steroids.

References

1. Lam CS, Umi Kalthum MN, Norshamsiah MD, Bastion M. Case series of children with steroid‐Induced glaucoma. Malays Fam Physician 2018 Dec 31; 13(3): 32–37.
Clinical effectiveness of combined cataract surgery with iStent inject implantation in the surgical treatment of open‐angle glaucoma
Authors: Gurbanzade Shakhriiar , Aghayeva Fidan , Assaf Abdelrahman , Lanzl Ines
Published: January 2024

Aims/Purpose: This study aims to evaluate intraocular pressure (IOP) change and reduction of topical IOP‐lowering medications after combined cataract surgery with iStentinject® implantation in the surgical treatment of open‐angle glaucoma.

Methods: Retrospective chart review of 100 patients (100eyes) with different types of open‐angle glaucoma (84% ‐ primary open angle; 16% ‐ pseudoexfoliation glaucoma), who were naïve to any previous ocular procedure and underwent combined cataract surgery with iStent®implantation, was performed. Study outcomes were median IOP change in the operated eye and the mean number of topical IOP‐lowering medications at 3, 6 and 12 months after surgery.

Results: The mean age of patients was 74 ± 7.5 years, 44% men and 56% women. The median pre‐ and postoperative IOP in the operated eye at 3, 6 and 12 months were 18.5(16–20) mmHg, 14.0 (12–16.75) mmHg, 14.5 (12–16) mmHg and 14.5 (12–16) mmHg, respectively. The median IOP change in the operated eyes at 3, 6 and 12 months follow up was −4 (−6 to −2) mmHg (p < 0.001), −4 (−6 to −1) mmHg (p < 0.001), and − 4 (−6.75 to −2) mmHg (p < 0.001), respectively. The higher the preoperative IOP level, the larger was the IOP‐lowering effect at different follow‐ups after surgery (−0.57, p < 0.001; −0.58, p < 0.001; −0.6, p < 0.001; at 3, 6 and 12 months, respectively). We found a statistically significant difference between the mean number of topical IOP‐lowering medications before and at 12 months after surgery (1.23 ± 0.8 vs. 1.08 ± 0.8; −3.42, p < 0.001).

Conclusions: This study shows a statistically significant IOP reduction at 3, 6 and 12 months after combined cataract surgery with iStent® implantation in glaucoma patients. The higher the preoperative IOP in the operated eye, the larger the IOP‐lowering effect after surgery at all follow‐ups. iStent inject, a minimally invasive glaucoma surgery approach is associated with the reduction of topical IOP‐lowering medications at 12 months follow‐up.

References (if any): Shalaby WS, Jia J, Katz LJ, Lee D. iStent inject: comprehensive review. J Cataract Refract Surg. 2021 Mar 1;47(3):385–399. doi: 10.1097/j.jcrs.0000000000000325.
Third surgery of Ahmed valve tube exposure: A case report
Authors: Fabra Yolanda Cifre , Prades Gemma Ortega , Parot Álvaro Andrés Ojeda , Pérez‐Torregrosa Vicente T. , Duch‐Samper Antonio M.
Published: January 2024

Aims/Purpose: Exposure of the glaucoma drainage devices tube is one of the main postsurgical complications, and it is important not to delay treatment in order to avoid serious situations such as endophthalmitis. Our aim is to report a case of a patient with an Ahmed valve tube exposure who had undergone two previous surgeries unsuccessfully.

Methods: We present the case of a 71‐year‐old male patient with diabetic retinopathy with an Ahmed valve in his left eye for 4 years due to neovascular glaucoma. In the first surgery the tube was positioned in the posterior chamber. After two months, displacement of the tube was observed so it was repositioned in anterior chamber with apposition of Ologen® on temporal, superior sclera. Three years later, exposure of the valve tube was seen and it was covered with Tutopatch® and conjunctiva. Recently, on examination, exposure of the valve tube was observed once again. We removed the epithelial cells from the scleral bed with absolute alcohol, after that we revitalized the conjunctival borders of the wound and covered the tube with fascia lata. Finally, we sutured the conjunctiva without tension.

Results: At the moment, the tube remains covered and the superior temporal conjunctiva has a good appearance.

Conclusions: Different repair techniques are described in the bibliography, such as conjunctiva covering, grafting of different materials, repositioning of the tube with grafting, valve removal and implantation in a different quadrant and even definitive removal of the valve. In our case we used a fascia lata graft, which is associated with a lower risk of subsequent exposure. The previous preparation of the scleral bed and the edges of the conjunctiva, as well as a conjunctival suture free of tension and traction are key to obtaining a good result.
Progression risk factors in glaucoma patients with disc haemorrhage
Authors: Lee Ji Young , Choi Jin A.
Published: January 2024

Aims/Purpose: In this study, we investigated the clinical characteristics of disc haemorrhage relating to hemodynamic factors and their impact on glaucoma progression.

Methods: This was a retrospective cohort study, including 81 eyes with open angle glaucoma accompanying DH. Eyes were classified as non‐recurrent DH and recurrent DH. Eyes with recurrent DH were sub‐classified into three groups according to the location of DH. Visual field progression was determined by event‐based analysis using the Guided Progression Analysis (GPA) software. The coefficient of variation (CV) of systolic and diastolic blood pressure (BP) was used to measure visit‐to‐visit variability. Kaplan–Meier survival analyses were used to compare the cumulative risk ratio of progression between groups.

Results: Recurrent DH group showed a significantly higher systolic and diastolic BP (p = 0.014 and 0.021, respectively), with higher proportion of VF progression (p = 0.019), compared to non‐recurrent DH group. Particularly, female with recurrent DH showed highest cumulative probability of VF progression (p = 0.047, Log‐rank test). Recurrent DH at a different quadrant showed a greater cumulative probability of VF progression than non‐recurrent DH group (p = 0.038, Log‐rank test). In the Cox regression analyses, higher visit‐to visit variability of diastolic BP, female gender, recurrence DH in a different quadrant significantly contributed the progression of glaucoma.

Conclusions: The presence of recurrent DH was associated with elevated systolic and diastolic BP, while increased visit‐to visit variability in diastolic BP was linked to the progression of glaucoma. Our study emphasize the role of hemodynamic factors in the pathogenesis of DH in glaucoma.
Brachial artery FMD and carotid artery IMT in glaucoma
Authors: Rogosic Veljko , Rogosic Lucija Vanjaka , Frankovic Andro , Kabic Sime
Published: January 2024

Aims/Purpose: The purpose of the study was to assess the ultrasound measurements of the brachial artery flow‐mediated dilation (FMD) and carotid artery intima‐media thickness (IMT) and their relationship in glaucoma patients.

Methods: Thirty‐seven patients with glaucoma and thirty‐one healthy controls were included in the study. All glaucoma patients and controls underwent ultrasound measurement of FMD of the brachial artery and ultrasound measurement of IMT of the carotid artery.

Results: The mean values of brachial FMD were significantly lower among the glaucoma compared with controls (15.3 ± 9.5% vs 19.8 ± 9.3%, p = 0.04). No significant difference was found in carotid IMT (1.2 ± 0.4 vs. 1.1 ± 0.3, p = 0.4), and brachial artery diameter at rest (4.7 ± 0.6 vs. 4.9 ± 0.3, p = 0.2) between the glaucoma patients and controls. The significant difference in brachial artery diameter in hyperemia between the glaucoma patients and controls (5.4 ± 0.6 vs. 5.9 ± 0.4, p = 0.002) was found. A negative correlation among brachial FMD and carotid IMT as well as among brachial FMD and brachial artery diameter at rest was found.

Conclusions: Impaired brachial FMD indicates presence of systemic vascular endothelial dysfunction in glaucoma; glaucoma patients with lower values of the brachial FMD are at increased risk of having thickened carotid IMT.
The impact of COVID‐19 on the wait times and severity of surgical glaucoma cases evaluated at a tertiary eye center
Authors: Zhang Huixin , McIntyre Sarah , Abu‐Dieh Anas , Toren Andrew
Published: January 2024

Aims/Purpose: COVID‐19 has caused shortages in health services worldwide. In Canada, this led to a relocation of medical staff, which paradoxically acted as potential barriers to access to care when considering the significant delays reported in elective surgeries. The purpose of this study was to assess the effect of pandemic related delays on the wait times and severity of surgical glaucoma cases in a single tertiary referral center in Quebec, Canada.

Methods: In this retrospective cohort study, 182 and 201 eyes of patients who underwent glaucoma surgery at Hôpital Saint‐Sacrement, Quebec City, between the periods of March 1 to June 30, 2019 (pre‐pandemic) and 2021 (pandemic), were included. Severity data included mean visual field deficit, intraocular pressure (IOP), number of drops, and preoperative best corrected visual acuity (BCVA). The times from referral to surgery (referral time) and from listing date to surgery (listing time) were calculated.

Results: Visual field deficit was −11.6 ± 7.7 dB in 2019 versus −11.6 ± 7.5 dB in 2021 (p = 0.92). Mean preoperative IOP was 21.1 ± 9.70 mmHg in 2019 versus 20.0 ± 9.52 mmHg in 2021 (p = 0.25). The mean MAVC in the affected eye was 0.60 ± 0.72 LogMAR in 2019 versus 0.55 ± 0.73 LogMAR (p = 0.07). The mean number of preoperative drop classes was 3 ± 1 in both groups (p = 0.56). The mean number of patients referred with oral glaucoma medication increased from 45 to 70 in 2019 and 2021 respectively (p = 0.03). Time to consultation was 122 ± 120 days in 2019 versus 144 ± 136 days in 2021 (p = 0.17), whereas time to list was 48 ± 57 days in 2019 versus 38 ± 43 days in 2021 (p = 0.05).

Conclusions: There were no statistically significant differences in the severity of surgical glaucoma cases operated on during the pandemic. Waiting list time decreased, possibly secondary to the prioritization of more urgent glaucoma cases over other ophthalmic surgeries. These reassuring data suggest that the barriers of the pandemic did not lead to a severe worsening of access to care for surgical glaucoma patients.

References

Felfeli, Tina et al. The ophthalmic surgical backlog associated with the COVID‐19 pandemic: a population‐based and microsimulation modelling study. CMAJ Open. vol.9 (4) 1063–1072. 23 Nov. 2021, https://doi.org/10.9778/cmajo.20210145
Comparison between optic nerve head minimal waist of the nerve fibre layer and retinal nerve fibre layer thickness with regard to angular distribution
Authors: Soderberg Per , Holm Jonatan , Kisonaite Konstancija , Yu Zhaohua
Published: January 2024

Aims/Purpose: To compare angular distribution of the minimal waist of the nerve fibre layer in the ONH, Pigment epithelium central limit‐Inner limit of the retina‐Minimal distance (PIMD) and Retinal nerve fibre layer thickness (Rnfl) in not pathological eyes.

Methods: Altogether, one eye from each of 17 subjects were included. SS‐OCT of the optic nerve head with vicinity was captured 3 times in each subject with Triton (Topcon, Japan). PIMD was resolved in 500 angles in the frontal plane. Rnfl‐angle estimates were provided by the Topcon software integrated over 30 degrees steps in the frontal plane. The corresponding PIMD steps were estimated by averaging the corresponding steps in the frontal plane. For each step, the 3 iterated captures were averaged. The mean difference between PIMD and Rnfl, respectively averaged over 2π radians was estimated. The angular distribution of PIMD‐angle and Rnfl‐angle were compared using cross correlation over ±130 degrees (+: upper half. ‐: lower half).

Results: The mean difference between PIMD and Rnfl estimates averaged over angle within subject and then over subjects was CIμ(0.95) = 228 ± 8 um (d.f. = 16). In 16/17 subjects the angular distribution in the upper half was correlated in 16/17 and in 16/17 the lower half was correlated. The lack of correlation for the upper and lower half, respectively, was present in different eyes.

Conclusions: The collection of nerve fibres in the ONH increases the thickness at the waist in the ONH on an average 2.8 times. The angular distribution of PIMD and Rnfl is usually completely correlated in not pathological eyes but deviations occur. Thicker PIMD than Rnfl provides a wider dynamic range for PIMD to detect change due to glaucoma.

References

1. Kisonaite K, Yu Z, Raeme F, Bendazzoli SB, Wang C, Söderberg PG Automatic estimation of the cross‐sectional area of the waist of the nerve fibre layer at the optic nerve head Acta Ophthalmol 2023; Online ahead of print.: 1–8, DOI:10.1111/aos.15698
Protective effects of neuropeptide Y treatment on retina in a mouse model of experimental glaucoma
Authors: Palanivel Viswanthram , Basavarajappa Devaraj , Gupta Vivek , Graham Stuart
Published: January 2024

Purpose: Neuropeptide Y (NPY) is an endogenous 36‐amino acid linear peptide with tyrosine residues on both ends of the molecule. Cumulative evidence suggests that NPY and its receptors in the CNS may be a potential neuroprotective targets in various degenerative conditions. This study aimed to investigate the protective effects of NPY in the retina in an experimentally induced glaucoma animal model.

Methods: Weekly intracameral microbead injections were performed to induce sustainably increased intraocular pressure (IOP) and NPY was administered intravitreally for 2 months. Wild‐type C57BL/6J mice (n = 40) were categorized into four major groups i) control, ii) control + NPY, iii) high IOP model, & iv) high IOP + NPY. Inner retinal function was evaluated by using positive scotopic threshold response (pSTR) amplitudes. Eye and optic nerve sections were then immunostained with pNFH (phosphorylated neurofilament heavy chain), GFAP (glial fibrillary acidic protein) and Iba‐1(Ionized calcium‐binding adaptor molecule 1) antibodies to understand the protective effects of NPY treatment.

Results: IOP elevation was observed in the microbead model (control, 10.5 ± 0.75; microbead, 27.35 ± 1.92 mmHg). Functional data revealed a significant decline in the pSTR amplitudes in high IOP conditions (p < 0.0001, n = 10) compared to the control group, and a significant increase in pSTR was observed in the high IOP + NPY group (p < 0.001, n = 10). Optic nerves stained with pNFH revealed a significant protective effect of NPY treatment against high IOP‐induced axonal damage (p < 0.01, n = 4). Increased GFAP expression observed in high IOP condition was significantly decreased with NPY treatment both in the retina (p < 0.001, n = 4) and optic nerves (p < 0.01, n = 4). Similarly, microglial activation evaluated by Iba‐1 expression was also significantly decreased by NPY treatment both in the retina (p < 0.01, n = 4) and optic nerves (p < 0.01, n = 4).

Conclusions: NPY treatment significantly reduced inner retinal functional loss and optic nerve damage against high IOP‐induced glaucomatous injury. NPY also reduced the microglial activation and reactive gliosis in experimental glaucoma. Our ongoing investigation will reveal specific NPY receptors activation and biochemical mechanism underlying these protective effects in the retina.
Primary open‐angle glaucoma and its relationship with smoking: A systematic review and meta‐analysis
Authors: Ramji Saajan , Daniel Sohail , Kailani Obeda
Published: January 2024

Aims/Purpose: Glaucoma is one of the major global causes of irreversible blindness. Numerous studies have investigated the relationship between smoking and (the risk of developing) primary open‐angle glaucoma (POAG), yet two prior meta‐analyses have reported contradictory findings. Consequently, the objective of this review is to provide a comprehensive update regarding the correlation between smoking and the occurrence of POAG.

Methods: This systematic review was registered on PROSPERO, ID: CRD42023409440. A comprehensive search was carried out on EMBASE, MEDLINE, and Web of Science databases, encompassing articles published up until May 2023. The inclusion criteria comprised studies that provided a statistical analysis exploring the association between smoking and primary open‐angle glaucoma (POAG) in adult populations. After eliminating duplicate entries, 1596 articles were subjected to initial screening based on their titles and abstracts, of which 148 articles underwent full text screening. Data were extracted by two independent authors, and meta‐analyses were completed using Revman (version 5.4) software.

Results: A total of 30 studies met the inclusion criteria, encompassing cohort, case–control and cross‐sectional studies. The combined participant population across these studies was estimated to be approximately 300 000, with over 7300 cases of POAG. The results of the meta‐analysis revealed that individuals classified as current smokers, past smokers, as well as those who had both current and past smoking histories exhibited no statistically significant association with the occurrence of POAG when compared to individuals who had never smoked.

Conclusions: Our meta‐analysis provides evidence to suggest that there is no causal relationship between smoking and primary open‐angle glaucoma (POAG). However, considering the detrimental effects of smoking on ocular health, it remains imperative to advise patients on smoking cessation.
Morphology‐function correlation using available clinical parameters describing retinal ganglion cells in glaucoma suspects
Authors: Kocurek Bartłomiej , Kociołek Katarzyna , Pacwa Anna , Smedowski Adrian
Published: January 2024

Aims/Purpose: To determine the morphology‐function correlation using optical coherence tomography (OCT), perimetry and photopic negative responses (PhNR) measurements in glaucoma suspects.

Methods: The results of 155 patients who underwent static 24–2 Humphrey visual field test (Optopol), OCT (Optopol) and PhNR (RETeval) examinations were analysed. Patients were divided into two subgroups according to the PhNR wave implicit time, at the minimum value (n = 114) or at 72 ms (n = 41). From perimetry, the mean deviation (MD) and pattern standard deviation (PSD) were analysed. From OCT, retinal nerve fibre layer (RNFL) thickness and ganglion cell complex (GCC) thickness were considered. From the PhNR test, the amplitude of the wave obtained using RETeval was analysed. For the correlation calculations, Spearman's test was used.

Results: There was a significant, moderate correlation observed between PhNR at minimum value and PSD (r = 0.2145, p = 0.0006); weak correlations observed between PhNR at minimum value and MD (r = −0.1456, p = 0.0203), RNFL (r = −0.1355, p = 0.0204), GCC (r = −0.1199, p = 0.0406). In case of PhNR at 72 ms, significant moderate correlations were observed for PhNR at 72 ms and PSD (r = 0.2863, p < 0.0001), (RNFL r = −0.2754, p < 0.0001) and (GCC r = −0.2709, p < 0.0001); weak correlation was observed for PhNR at 72 ms and MD (r = −0.1662, p = 0.0219).

Conclusions: Based on our analysis, it seems that PhNR at 72 ms correlates better with Retinal Ganglion Cells morphological measures in OCT (GCC and RNFL) and PhNR at minimum value correlates selectively with visual function measured with perimetric PSD exclusively, thus PhNR at minimum value may be more accurate coefficient to be used as a substitute of perimetric parameters.
What artificial intelligence can bring us in the diagnosis and progression of glaucoma
Authors: Ettouri Sara , Ghizlane Daghouj , Benchekroun Reda , El Hadi Kawtar , Lamiaa Arab , el Maaloum Loubna , Allali Bouchra , El Kettani Asmaa
Published: January 2024

Aims/Purpose: Our goal is to focus on the contribution of artificial intelligence in glaucoma from diagnosis to progression.

Methods: By a literature review, we will review work using AI in the field of glaucoma, whether for screening, diagnosis or detection of progression.

Results: For the diagnosis: Recently, two papers were published reporting results of DL algorithms to diagnose glaucoma from Visual Field data. Several authors have evaluated AI‐based fundus photograph analysis for its utility for detecting glaucoma such as the study of Liu et al which grouped 241 032 images of 68 013 patients with a sensitivity of 96.2% and specificity of 87.2% also for analysing OCT imaging data from peripapillary RNFL thickness maps and the macular ganglion cell complex for discriminating between glaucomatous and normal eyes with AROC values ranging from 0.69 to 0.99. Prediction of IOP trends from previous data and medications would be a useful and plausible use of AI. For the progression of glaucoma: Multiclass support vector machines (SVMs), have been used to simultaneously discriminate between normal, non progressing, and progressing eyes through the analysis of confocal scanning laser ophthalmoscopy (CSLO) images with a correct classification rate of 88% .

Conclusions: Many AI strategies have shown promising results for glaucoma detection using fundus photography, optical coherence tomography, or automated perimetry. The combination of these imaging modalities increases the performance of AI algorithms, with results comparable to those of humans. Research in the coming years will need to address unavoidable questions regarding the clinical significance of such results and the explicability of the predictions.

References

1. Mursch‐Edlmayr AS, Ng WS, Diniz‐Filho A, Sousa DC, Arnold L, Schlenker MB, et al. Artificial Intelligence Algorithms to Diagnose Glaucoma and Detect Glaucoma Progression: Translation to Clinical Practice. Transl Vis Sci Technol. 15 oct 2020.

2. Li Z, He Y, Keel S, Meng W, Chang RT, He M. Efficacy of a Deep Learning System for Detecting Glaucomatous Optic Neuropathy Based on Color Fundus Photographs. Ophthalmology. août 2018.
Artificial intelligence in glaucoma progression: A systematic review
Authors: Guirao‐Navarro Maria Concepcion , Lim Hong Kai , Antunes Diandra , Suribhatla Rhea , Jutley Gurjeet
Published: January 2024

Aims/Purpose: Glaucoma is the leading cause of irreversible blindness worldwide. Effective assessment of glaucoma progression could facilitate timely interventions and improve prognosis. This systematic review aims to evaluate the use of machine learning (ML) in the detection and prediction of longitudinal glaucoma progression.

Methods: An online search was conducted on 31.12.2022, and relevant studies were identified. Outcomes included ML maximum sensitivity, specificity and area under the curve (MSSAUC) (mean (range)).

Results: Of the 577 records initially identified, 40 studies with over 156 000 eyes were included. Overall, 30 studies included traditional ML methods, and 13 studies included representational methods. 28 studies used supervised ML, whilst 12 studies used unsupervised ML. 27 studies performed classification, and 16 studies included regression analysis. 11 studies evaluated structural glaucoma data, such as retinal nerve fibre layer thickness. Six studies detected glaucoma progression, with pooled MSSAUC of 68.9% (36.9–86.0), 80.5% (49.0–94.0) and 0.80 (0.60–0.91). Five studies predicted glaucoma progression, with pooled MSSAUC of 84.9% (81.0–93.0), 73.5% (59.0–91.7) and 0.82 (0.71–0.90). 23 studies evaluated functional visual field data. 10 studies detected glaucoma progression, with pooled MSSAUC of 74.8% (3.8–95.0), 94.3% (90.0–98.1) and 0.89 (0.82–0.94). Four studies predicted glaucoma progression, with pooled MSSAUC of 52.2% (20.0–72.0), 72.3% (49.0–95.0) and 0.73 (0.44–0.86). Eight studies combined structural and functional data. Two studies detected glaucoma progression and six studies predicted glaucoma progression, with pooled MSSAUC of 66.6% (44.2–83.7), 90.0% (85.0–100%) and 0.79 (0.61–0.88).

Conclusions: ML detection and prediction of longitudinal glaucoma progression is highly accurate. However, there is significant heterogeneity in ML methodologies. Standardization is needed for robust evidence of the clinical utility of ML.
Syndromic congenital glaucoma clinical features and therapeutic results
Authors: Imad Hanane , Assia E. L. Harrar , Alaoui Hamza , Daghouj Ghizlane , Loubna El Maaloum , Bouchra Allali , Asmaa El Kettani
Published: January 2024

Aims/Purpose: The objective is to study the clinical particularities and the results therapies.

Methods: This is a retrospective study of 15 children (25 eyes) since 2012 until 2021 at the paediatric ophthalmology department of the August 20 hospital from Casablanca‐Morocco.

Results: In our study, there were 15 cases including 9 cases (13 eyes) of syndrome of Sturge weber Krabb, 2 cases (4 eyes) of Axenfield Reiger syndrome, 2 case (4 eyes) of Peters syndrome 1 case (2 eyes) of lower syndrome, 1 case (2 eyes) of polymalformative syndrome (cardiopathy, pulmonary stenosis, bilateral femoral epiphyseal dysplasia). The average age is 8 years with a sex ratio of 1.7, the notion of inbreeding exists in 43%. The warning sign was buphthalmos in 72% of cases, on clinical examination the cornea was edematous in 60% of cases with an average diameter 13.2 mm corneal, with anterior iris synechiae in 32% of cases, bilateral cataract in 4% of cases, persistence of primary vascularization in 4% of cases and an average of excavation of 7/10, an average TO at 34 mmHg. The most common systemic abnormalities were facial angioma (56%), epilepsy (41%) and mental retardation (30%).Treatment was trabeculectomy in 96% of cases associated with medical treatment in 100% of cases.

Conclusions: It is a rare, blinding pathology, the clinical forms of which are numerous with complex ocular and general malformations, which can pose etiological and therapeutic problems that are difficult.

References

1. Kenyon KR. Mesenchymal dysgenesis in Peters' anomaly, sclerocornea and congenital endothelial dystrophy. Exp Eye Res 1975; 21: 125–42.

2. Trans Am Ophthalmol Soc 1958; 56: 507–70 ‐ PubMed.
Synergistic effect of mesenchymal stem cells and silver nanoparticles in the treatment of retinal degenerative diseases
Authors: Palacká Kateřina , Hermankova Barbora , Javorkova Eliska
Published: January 2024

Aims/Purpose: Retinal degenerative diseases represent one of the leading causes of visual loss. Mesenchymal stem cells (MSCs) provide potential option for the treatment of several type of pathologies, including ocular diseases. Moreover, silver nanoparticles (AgNPs) are currently widely used in various fields of medicine mainly due to their antibacterial and antiangiogenic properties. Several studies showed their beneficial but also harmful effect. However, there are limited information about the synergistic effect of AgNPs with MSC‐based therapies.

Methods: Chronical retinal degeneration was induced in BALB/c mice by repeated intraperitoneal application of sodium iodate (NaIO3). MSCs, AgNPs or MSCs plus AgNPs were intravitreally injected 48 h before the last application of NaIO3. Retinas were isolated after additional 7 days and tested by RT‐PCR for the expression of genes for rhodopsin (photoreceptors), Iba‐1 (microglia/macrophages), IL‐1β and galectin‐3. The presence of MSCs stained with PKH‐26 was analysed by flow cytometry.

Results: It was shown that MSCs and MSCs applied with AgNPs were still present in the retina on day 7 after application. In all treated groups, the expression of the gene for galectin‐3 was decreased in contrast to untreated control. However, co‐application of MSCs with AgNPs had limited effect on downregulation of Iba‐1 and IL‐1β in contrast to MSCs or AgNPs treated group.

Conclusions: The application of MSCs and AgNPs modulated immune response in chronical retinal degeneration but co‐application of MSCs with AgNPs decreased immunoregulatory effects comparted with single‐component therapy. Thus, there is a need for more investigation focusing on potential changes in MSCs applied with AgNPs.
Retinal microcirculatory parameters ‐ Clinical applications beyond ophthalmology
Authors: (Boy) Houben A. J. H. M.
Published: January 2024

Microvascular dysfunction (MVD) is known as a classical complication of diseases like diabetes and hypertension. However, MVD is also known as a cause in the (early) development of cardiovascular and metabolic diseases. In addition, MVD has been shown to be associated with cardiovascular mortality.

Measuring MVD in‐vivo is demanding, and, therefore, a broad application of these techniques in clinical studies has been lacking. One exception in this regard is analysing microvascular function in images of the retina. Many studies in various cohorts have consistently shown for instance that reduced retinal microvascular diameters are not only associated with current high blood pressure, but are also associated with as increased risk for developing hypertension in the future. Similar findings, changed diameters and risk prediction, have been found for diabetes.

In the present lecture, an overview will be presented on the latest concepts and examples of retinal microvascular changes in structure and function in relation to cardiovascular and metabolic diseases.
Emerging therapies for geographic atrophy
Authors: Grzybowski Andrzej
Published: January 2024

Geographic atrophy (GA) is a late‐stage form of age‐related macular degeneration (AMD) characterized by progressive degeneration of photoreceptors, retinal pigment epithelium (RPE), and choriocapillaris primarily in the macula. It was shown in AREDS studies that supplementation of high‐dose antioxidant vitamins (C, E, and beta‐carotene) and zinc, decrease the risk of progression to advanced AMD.

It was suggested that the complement system, a part of the human immune system, plays an important role in the GA pathophysiology. Different complement genes have been linked to AMD in genome‐wide association studies, and the odds of GA were estimated to be 2.5 times higher per copy of a common risk allele (Y402H) of the CFH gene in individuals of European ancestry. In histologic studies complement proteins were found in drusen as well as elevated levels of complement proteins in the outer retinal tissue of postmortem eyes with AMD. Moreover, higher levels of activated complement products in plasma have been found in GA patients. Thus, several treatments targeting the complement system are investigated. The drugs that showed phase 3 efficacy and safety include pegcetacoplan and avacincaptad pegol, which are complement C3 and complement C5 inhibitors, respectively.
Is there a role for genetic testing in AMD care?
Authors: Schwartz Stephen G.
Published: January 2024

Age‐related macular degeneration (AMD) is a complex genetic disease. At this time, there are over 50 variants in over 30 genetic loci that are associated with various aspects of the disease. The two best studied groups of risk alleles are related to complement factors (especially Complement Factor H or CFH) and the Age‐related Maculopathy Susceptibility 2 (ARMS2)/High‐temperature Requirement A Serine Peptidase 1 (HTRA1) complex. In the opinion of the presenter, at this time there is no convincing evidence of an association between AMD risk allele genotype and clinical outcomes. Therefore, while genetic analysis remains an intriguing area of research, there is currently no role for genetic testing in the routine clinical care of AMD patients.
Inflammatory response of both retinas and superior colliculi to unilateral optic nerve axotomy
Authors: Galindo‐Romero Caridad , Cabrera‐Maqueda José María , Boia Raquel , Lucas‐Ruiz Fernando , González‐Riquelme María José , Ambrósio António Francisco , Santiago Ana Raquel , Vidal‐Sanz Manuel , Agudo‐Barriuso Marta
Published: January 2024

Objective: Unilateral optic nerve crush (ONC) induces a bilateral inflammatory reaction affecting both injured and contralateral un‐injured retinas. However, few works have investigated the spread of inflammation along visual pathway. Our aim was to study the glial response and the underlying molecular changes in both retinas and the superior colliculi (SCi), the main projection areas of retinal ganglion cells in mice. In this species, >90% of RGCs project to the contralateral SC (cSCi).

Methods: The left optic nerve of adult pigmented C57Bl/6 male mice were crushed (ONC) at 0.5 mm from the optic disk or underwent surgery without crushing (Sham). One group of intact mice was used as controls. Two studies were carried out:

1) At 1, 3, 9 and 30 days post lesion (dpl) both retinas and SCi were freshly dissected and their RNA extracted. Using qPCR we measured the expression levels of TGF‐β1, IL‐1β, TNF‐α, Iba1, GFAP, MHC II and TSPO in retinas and SCi. In SCi extracts we also studied Casp3, CXCR1, Lcn2, IL‐6, CD206, IL‐4, and AQ4. Hptr and Gapdh were used as houskeepings. Intact retinas and SCi were used as controls.

2) Three, 9 and 30 days after ONC or sham‐surgery immunodetection of microglia and macroglial cells was carried out in sagittal brain sections. The area occupied by GFAP and MHC II signal as well as the density of Iba1+ and CD68+ cells was quantified in both SCi. Intact brains were used as controls.

Results: Sham surgery alone modified gene expression in both retinas and SCi compared to intact animals. Therefore, to isolate the effect of ONC, we compared ONC vs. Sham. After ONC, TNF‐α upregulated early in both retinas and IL‐β remained overexpressed in injured retina at day 30. GFAP overexpression was exclusively observed in injured retina while Iba1 overexpression was presented in both. TSPO and MHCII and Casp3 overexpression was observed only in the cSC.

Anatomical microglial activation (rounded somas and CD68 expression) was observed in the cSC from day 3 onwards after ONC. In the ipsilateral SC (iSC) microglial cells did not show signs of activation. Astrocytes hypertrophied in both SCi from day 9 after ONC, but this response was also observed in Sham‐animals.

Conclusions: Sham surgery promotes an inflammatory and glial response that must be considered in experimental designs. Unilateral ONC triggers a bilateral response which extends anterogradely and retrogradely along the visual pathway.
Nutraceutical supplementation in inherited retinal dystrophies
Authors: Velasco Sheyla , Olivares‐González Lorena , Morales Silvia , Valencia Daira , Esteban‐Medina Marina , Loucera Carlos , Salom David , García Emilio González , del Castillo Jose Miguel Soriano , Rodrigo Regina
Published: January 2024

*Correspondence: rrodrigo@cipf.es; Tel: (+34 96 328 96 80)

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy causing progressive vision loss. Ocular redox status is altered in RP suggesting oxidative stress could contribute to their progression. In addition, it is accompanied by chronic and sustained inflammation, including M1 microglia activation. In our group we evaluated, both the effect of a mixture of nutraceuticals with antioxidant properties (NUT) and the effect of an essential fatty acid (EFA) supplement containing specialized pro‐resolving mediators (SPMs) on retinal degeneration in rd10 mice, a model of RP.

Both compounds were orally administered to mice from postnatal day (P)9 to P18. At P18, the electrical activity of the retina was examined by electroretinography (ERG) and innate behaviour in response to light were measured. Retinal degeneration was studied via histology including the TUNEL assay and microglia immunolabelling. Microglia polarization (M1/M2) was assessed by flow cytometry, qPCR and histology. Redox status was analysed by measuring antioxidant enzymes and markers of oxidative damage.

Interestingly, the NUT and EFA supplements ameliorated retinal dysfunction and degeneration by improving ERG recording and sensitivity to light, and reducing photoreceptor cell loss.

The supplement reduced inflammation and microglia activation attenuating M1 markers as well as inducing a shift to the M2 phenotype in rd10 mouse retinas. These supplements also reduced oxidative stress markers of lipid peroxidation and carbonylation. These findings could open up new therapeutic opportunities with oral supplementation.
Keratitis fugax Hereditaria caused by a pathogenic variant in NLRP3
Authors: Turunen Joni
Published: January 2024

Keratitis fugax hereditaria (KFH, MIM 148200) is an autosomal dominant periodic corneal autoinflammation caused by a single pathogenic variant c.61G>C (rs200154873) in the NLRP3 gene. NLRP3 protein is a key component of the NLRP3 inflammasome, which activation leads to the secretion of IL‐1 beta and IL‐18 leading to inflammation. KFH is characterized by periodic unilateral attacks causing pain, redness, and reduced vision. Repeated attacks lead to permanently reduced visual acuity in a subset of the patients. Currently, we have examined 94 individuals with KFH from 26 families. Age of onset varied from 6 to 20 years (median, 11). During the acute attack symptoms were eye pain, photophobia, conjunctival injection, and foreign body sensation. Half of the patients (48%, n = 45) developed corneal oval opacities. KFH was most often misdiagnosed as anterior uveitis (26%, n = 24), conjunctivitis (13%, n = 12), recurrent erosion (11%, n = 10), and herpetic keratitis (10%, n = 9). Geographically, KFH is most prevalent in Finland and Sweden according to allele frequencies in gnomAD, 0.014% in Finland and 0.011% in Sweden. Patient‐derived peripheral blood mononuclear cells are more prone to secrete IL‐1β after NLRP3 inflammasome stimulation, confirming that the c.61G>C is a gain‐of‐function variant. Furthermore, prednisolone is a potent drug to reduce IL‐1β secretion in the cell culture. We recommend prednisolone for the treatment of acute attack, and for permanently reduced vision due to corneal opacities and thinning, scleral contact lenses are the first‐line treatment. KFH is underrecognized and misdiagnosed corneal disease and should be recognized at least in the Scandinavian population.
OCT biomarkers in wet type age related macular degeneration
Authors: Hassan Nihal
Published: January 2024

OCT technology is evolving very quickly, and new retinal biomarkers are continuously described. Optical coherence tomography (OCT) is the most widely used technology for the diagnosis and follow‐up of AMD patients, which is widely used to study and guide the clinical approach, as well as to predict and evaluate treatment response.

OCT biomarkers in wet type age related macular degeneration can be divided into two different categories.

Biomarkers based on the retinal distribution of fluids and, structural biomarkers based on the presence or absence of specific features can be observed in the retinal layers, choroid, or vitreomacular interface.

The aim of this review is to describe and analyse various structural OCT‐based biomarkers, which have practical value during both initial assessment and treatment follow‐up of wet type AMD patients.

Central retinal thickness has been the most common and one of the first OCT identified biomarkers, today, other qualitative and quantitative biomarkers provide novel insight into disease activity and offer superior prognostic value and better guidance for tailored therapeutic management.

The key importance of retinal fluid compartmentalization (intraretinal fluid, subretinal fluid, and subretinal pigment epithelium (RPE) fluid).

In the second part, the structural alterations of different retinal layers in various stages of the disease (photoreceptors layer integrity, hyperreflective dots, outer retinal tubulations, subretinal hyperreflective material, and retinal pigment epithelial tears) will be analysed in detail.

The last part of the review will focus on how alterations of the vitreoretinal interface (vitreomacular adhesion and traction) and of the choroid (sub‐RPE hyperreflective columns, pre‐choroidal clefts, choroidal caverns, choroidal thickness and choroidal volume, and choroidal vascular index) interact with AMD progression.

This up‐to‐date review article provides a comprehensive description on how structural OCT‐based biomarkers provide a valuable tool to monitor the progression of the disease and the treatment response in AMD patients.