bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors contributing to the development of choroidal microvasculature dropout in glaucoma suspects and patients with glaucoma
Authors: Shin Hee Jong , Park Chan Kee , Park Hae‐Young
Published: January 2024

Aims/Purpose: We aimed to characterize and compare the occurrence of MvD between glaucoma suspects and patients with glaucoma. In addition, the factors related to the development of parapapillary MvD in glaucoma suspects and patients with glaucoma were investigated.

Methods: Total 150 eyes, 68 eyes of glaucoma suspects and 82 eyes of glaucoma patients were analysed in this study. Disc photography, VF, OCT, HRT, OCTA examinations were performed every year. Student's t‐test and the χ2 test were used to compare continuous and categorical variables, respectively. Slope of OCT, HRT, and VF parameters were calculated as change per year using linear regression. Univariate and multivariate logistic regression analyses were used to identify factors associated with MvD development.

Results: Comparison between group who developed MvD and group without MvD, there was a significant difference in the slope of cup volume by OCT, central VF progression, and ONH surface depression measured by HRT. Thinner baseline GCIPL thickness, central VF progression, and the slope of cup shape measures by HRT were found to be significant associated factors to MvD development in multivariate analysis in total subjects. In the regression analysis of glaucoma suspect group, greater axial length and baseline cup volume among the baseline factors and the slope of GCIPL thickness and central VF progression among follow‐up factors were significantly associated with the MvD development. In the glaucoma group, central VF progression and ONH depression among follow‐up elements were observed as significant factors and the baseline factor had little relationship.

Conclusions: MvD appears not only as a result of the progression of axonal loss of RGC in glaucoma but may also be developed by structural changes and mechanical susceptibility of the ONH associated with baseline characteristics, including myopia, thin central corneal thickness, and higher baseline IOP. Analysing the structural susceptibility of the ONH can predict the occurrence of MvD, which is can be helpful in predicting the progression of glaucoma.
Retinal neurodegeneration in intraocular pressure fluctuation rat model
Authors: Park Chan Kee , In Jung Kyoung , Han Jeong‐Sun
Published: January 2024

Aims/Purpose: The role of IOP fluctuation is controversial in development and progression of glaucoma in clinical trials. We investigated effects of intraocular pressure fluctuation on retinal neurodegeneration and their mechanisms in rats.

Methods: Male Sprague–Dawley rats were treated with IOP‐lowering eyedrops (brinzolamide and latanoprost) or saline for 8 weeks. IOP‐lowering eyedrops were put on Monday and Thursday for the irregular instillation group or daily for the regular instillation group, and saline was put daily for the control group. IOP was measured daily under general anaesthesia using a rebound tonometer. Oxidative stress, reaction of microgliosis and the number of retinal ganglion cells (RGCs) were measured.

Results: Mean IOP was lower both in the irregular instillation group (9.6 ± 0.4 mmHg) and the regular instillation group (9.5 ± 0.4) than the control group (10.1 ± 0.4 mmHg, p < 0.001). Standard deviation (SD) of IOP was higher in the irregular instillation group (0.8 ± 0.1 mmHg) than the regular instillation group (0.5 ± 0.1 mmHg) or the control group (0.6 ± 0.3 mmHg, p < 0.001). Oxidative stress measured by dihydroethidium, oxidative DNA damage exhibited by 8‐hydroxy‐2′‐deoxyguanosine, and immunostaining for nitrotyrosine were upregulated (All p < 0.001). Expression of glial fibrillary acidic protein in the optic nerve head was more increased in irregular instillation group than the control group, but not in the regular instillation of eyedrops (p = 0.001). Expression of anti‐ionized calcium binding adaptor molecule (Iba‐1), a marker for microglia and P2Y12 known as a chemotactic receptor for microglia did not show a significant difference between the irregular instillation group and the control group. Expression of cleaved caspase‐3 was greater in the irregular instillation group than other two groups (p < 0.001). The number of RGCs stained with anti‐Brn3a antibody was lower in the irregular instillation group than other two groups (p = 0.002).

Conclusions: IOP fluctuation induced by treatment of irregular instillation of IOP‐lowering eyedrops reduced the number of RGCs. Our findings indicate that IOP fluctuation induced by treatment of irregular instillation of IOP‐lowering eyedrops could lead to degeneration of RGCs probably by increasing oxidative stress and microgliosis.
Evaluating the diagnostic performance with neurovascular segregation of the retinal nerve fibre layer in glaucoma
Authors: Wong Damon , Yow Ai Ping , Chua Jacqueline , Schmetterer Leopold
Published: January 2024

Aims/Purpose: To evaluate the diagnostic performance in detecting eyes with glaucoma by segregating the neuronal and vascular components in circumpapillary optical coherence tomography (OCT) and OCT angiography (OCTA) scans.

Methods: In this study, 93 participants with glaucoma were age‐ and gender‐matched with normal controls with no ocular diseases. OCT and OCTA volumetric images of one eye from each participant were acquired using a prototype high resolution swept source OCT imaging system (Zeiss PlexElite) using a 6 mm x 6 mm imaging protocol centered at the optic nerve head. Circumpapillary OCT and OCTA images with a diameter of 3.46 mm were subsequently generated. Information from the circumpapillary and enface OCTA images were used to isolate and segregate the vascular components from the circumpapillary retinal nerve fibre layer (RNFL), which was obtained using a deep learning segmentation approach. Thicknesses of the RNFL with and without the vascular components were measured and diagnostic performance was evaluated using area under the receiving operating characteristic curve (AUC) analysis. Both global and quadrant (superior, inferior, nasal and temporal) measurements around the optic nerve head were considered.

Results: Imaging data of one eye from 154 healthy and 143 glaucoma participants were acquired. Using only the global RNFL thickness, the detection of glaucoma achieved an AUC of 0.877 ± 0.021. With the vascular components excluded from the global RNFL thickness, an AUC of 0.890 ± 0.020 was obtained. When the vascular and non‐vascular components of the RNFL in the different quadrants were modelled separately, AUC improved to 0.927 ± 0.015, and was found to be significantly higher than the detection of glaucoma using global measures (p < 0.001).

Conclusions: Segregation of vascular and non‐vascular components in the retinal nerve fibre layer led to an improvement in glaucoma detection. Further improvements were observed when the contributions of the components in the RNFL quadrants were modelled separately.
Central contrast sensitivity as an outcome measure in randomized controlled trials in glaucoma ‐ a systematic review
Authors: Møller Jens Riis , Sverstad Alexander , Virgili Gianni , Azuara‐Blanco Augusto , Freiberg Josefine Clement , Ahrensberg Simone , Kristianslund Olav , Petrovski Goran , Kolko Miriam
Published: January 2024

Aims/Purpose: Standard automated perimetry (SAP) is currently the gold standard for diagnosing and assessing glaucoma progression. However, contrast sensitivity (CS) has shown promise as a valuable diagnostic tool in the early stages of glaucoma. This study aims to describe the evaluation of central CS as an outcome measure in randomized controlled trials on glaucoma.

Methods: A descriptive systematic review was conducted, searching multiple databases for relevant literature and abstracts. Two independent authors screened the records and collected data, with a third reviewer available for resolution in case of disagreements. Eligibility criteria included the use of central CS as an outcome measure, publication in English with no restrictions on the date, glaucoma of any type (including suspects and ocular hypertension), and no limitations on age, sex, ethnicity, or geographical location. Any type of intervention and comparator was included, while animal studies were excluded.

Results: The initial search yielded 990 articles and abstracts for title and abstract screening, of which 29 met the eligibility criteria for full‐text data extraction. The review is currently in progress.

Conclusions: Glaucoma affects not only peripheral visual functions but also central visual functions in the early stages. SAP detects visual field defects only after a significant loss of retinal ganglion cells. Visual acuity (VA) is routinely used in glaucoma evaluation but provides limited information on the disease stage, focusing mainly on foveal involvement. Currently, there are no widely accepted examinations of central visual functions routinely performed for suspected or established glaucoma patients. Studies have shown that CS declines in the early stages of glaucoma. This review aims to provide insight into the tests used to assess CS in glaucoma and their performance.
Risk factors and macular microvascular changes in open angle glaucoma progression: A longitudinal study using OCT‐A
Authors: del Mar Schilt‐Catafal Maria , Pérez‐Torregrosa Vicente T. , Duch‐Samper Antonio M.
Published: January 2024

Aims/Purpose: To investigate prospectively macular microvascular changes in patients with glaucoma and identify common characteristics among the progressive eyes.

Methods: A 12‐month prospective longitudinal study was performed with 124 open‐angle‐glaucoma‐eyes (GE). Glaucomatous progression was defined as a decrease of ≥5 μm in average or ≥7 μm in a sector of RNFL thickness. OMAG OCT microangiography (Angioplex, HD OCT, Cirrus 5000, Zeiss) was used to analyse the macular region. The statistical analysis was performed using the SPSS version 23.0 statistical package (SPSS Inc., IL).

Results: Among the GE group, 22.36% of eyes showed progression, being the decrease of the Complete Region Macular Vessel Density (MVD) and Macular Capillary Perfusion Density (MPD) greater (−1.14 mm/mm2 and −3.18%) compared to non‐progressive eyes (−0.42 mm/mm2 and −1.02%) [p = 0.123 and 0.057], being the temporal and superior sectors for both MVD and MPD, the ones that showed greater differences (−1.44 mm/mm2, −1.11 mm/mm2, −3.6% and −2.95% respectively) [p > 0.05 for all]. Characteristics as elevated intraocular pressure (IOP) (17.29 vs 14.87 mmHg), thinner central corneal thickness (CCT) (521.53 vs 538.65 μm) and lower ocular perfusion pressure (OPP) (45.88 vs 49.21 mmHg) were significantly different in those progressive GE [p < 0′05 for all]. Nevertheless, increased vertical cup to disc ratio (CDV) (0.64 vs 0.63) and minimum ganglion cell layer thickness (GCLM) (58,82 vs 56.51 μm) were not significantly different in progressive GE [p = 0.768 and 0.249].

Conclusions: Data showed that when glaucomatous progression took place, stronger vascular changes occurred in the macular area, as greater decrease of MVD and MPD specially in the temporal and superior sectors. In addition, common characteristics as elevated intraocular pressure, thinner central corneal thickness and lower ocular perfusion pressure were identified in progressive GE. Nevertheless, further research with larger population and larger follow‐up is needed to obtain stronger results.
Fluvoxamine supresses transforming growth factor beta‐2‐induced fibrotic changes in trabecular meshwork cells
Authors: Medveczki Timea , Tran Minh N. , Besztercei Balazs , Torok Gyorgy , Kovacs Illes , Szabo Attila J. , Fekete Andrea , Hodrea Judit
Published: January 2024

Aims/Purpose: Primary open‐angle glaucoma is the leading cause of blindness worldwide, but no definitive treatment is available. Fibrotic‐like changes of trabecular meshwork (TM) results in increased stiffness and impaired outflow leading to increased IOP. Transforming growth factor‐β2 (TGF‐β2), a main driver of eye fibrosis, is increased in the aqueous humour of glaucoma patients. Recently, we proved that the specific sigma‐1 receptor agonist fluvoxamine (FLU) is antifibrotic in the kidney but its role in the TM is unknown. Therefore, we investigated the effects of FLU on the TGF‐β2‐induced fibrotic response in TM cells.

Methods: Fibrosis of the AS was induced in C57BL/6J mice by intracameral TGF‐β2 injection. AS were collected and F‐actin was visualized with Phalloidin and detected with confocal microscopy. The effect of FLU on TGF‐β2‐induced cell proliferation, cytoskeletal rearrangement, and fibrosis‐related proteins was investigated by MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide) assay, Phalloidin staining and Western blotting, respectively.

Results: TGF‐β2 injection resulted in F‐actin enhancement in vivo, indicating fibrotic‐like changes. In vitro, TGF‐β2 induced cytoskeletal rearrangement with increased F‐actin‐ bundles and clumps formation (p < 0.001) which were reduced by FLU (p < 0.001). Furthermore, FLU also inhibited cell proliferation (p < 0.05) in TGF‐β2‐treated cells. The profibrotic protein levels of connective tissue growth factor, fibronectin and collagen type IV were elevated by TGF‐β2 treatment (p < 0.001), while FLU prevented the elevation of these elements (p < 0.01; p < 0.001). FLU also hindered the TGF‐β2 caused decrease of Matrix Metalloproteinase‐2 (p < 0.05) thus facilitating ECM degradation.

Conclusions: FLU may reduce the fibrotic response of trabecular meshwork and could be a potential candidate for the treatment of fibrosis‐induced ocular hypertension.

Grants: OTKA‐ K135398, LP2021‐3/2021, TKP2021‐EGA‐24, Stipendium Hungaricum.
2 Year results of combined phacoemulsification‐ iStent inject W, from a single centre
Authors: Tsakiris Kleonikos , Gialelis Themistoklis , Vergados Athanasios
Published: January 2024

Aims/Purpose: Our aim is to review the 2 year results of combined phacoemulsification and iStent inject W implantation in a single centre in East London.

Methods: Patients were listed for surgery when cataract surgery was needed and further control of glaucoma was necessary. Electronic medical records were reviewed of all the patients who underwent the procedure in the period ranging from May 2018 until February ‘21. 87 eyes of 77 patients were identified, 3 eyes were lost to follow up in year one and 2 year data were obtained for 17 eyes. Vision, iop, drop dependency was measured and complications were recorded. Further surgical treatment was considered failure and the patient was then removed from the cohort.

Results: Mean vision improved from LogMAR 0,45 to 0,16 stable throughout the two years. Drop dependency dropped modestly from 2,71 to 2,49 (8%) in year one and 2,35% (13,04%) in year two. IOP dropped from 19,25mHg to 14,55 mmHg (24,43%) in year one and 12,41 mmHg (36,68%) in year two. Complications included one patient with retained lens matter, 1 with recurrent uveitis, 1 iris prolapse, 1 Irvine Gass syndrome,1 had steroid response and 2 had pressure spikes. Furthermore by year 2, 1 patient was excluded due to incomplete documentation, 2 were discharged, 4 died (6 eyes), 4 patients needed further treatment with trabeculectomy and one received micropulse cyclodiode laser.

Conclusions: Overall combined phacoemulsification/iStent inject W surgery is safe, effective, does not affect the overall safety profile of phacoemulsification surgery and has a place in early and moderate glaucoma. Improvement in year 2 results in comparison to year one can be explained by the removal from the study of the patients that received further treatment; and the small number of patients seen is an effect of the reduced capacity because of the COVID‐19 pandemic restrictions during that time.
The socioeconomic impact among Tunisian glaucoma patients
Authors: Jallouli Aida , Maamouri Rim , Doukh Meryem , Aoun Hichem , Ouederni Meriem , Cheour Monia
Published: January 2024

Aims/Purpose: The purpose of our study is to evaluate the socioeconomic impact of primary open‐angle glaucoma (POAG) on Tunisian population.

Methods: A cross‐sectional study was conducted in Habib Thameur Hospital, Tunisia. POAG patients who were ≥ 40 years old at the time of recruitment had minimal cataract, underwent cataract or trabeculectomy surgery at least 3 months prior and were on medical treatment. Data were collected from patients through one‐on‐one interview with questionnaire.

Results: We collected 38 glaucomatous patients; the mean age of patients was 58 years old (range 46–82 years). There was a female predominance (57.89%) with a sex ratio (M/F) of 0.72. The average of intraocular pressure (IOP) was 21.6 mmHg with 21.05% of patients having an IOP over 30 mmHg. We noted that 76.31% of patients resided in urban areas and 41.2% of them were illiterate. The monthly income as claimed by patients ranged between zero and 600 Tunisian dinars (TND) with an average monthly income of 287.5 TND. Patients' monthly spending on glaucoma ranged between zero and 69.5 TND, with a mean of 35.2 TND which equalled 12.2% of their monthly income. Eighteen (47.3%) of the participants experienced anxiety and depression. Severe stage of glaucoma and reduced visual acuity were significantly associated with anxiety and depression.

Conclusions: Identifying the socio‐economic impact of glaucoma can raise awareness among Tunisian patients and ophthalmologists, and may result in the optimal management of glaucoma.
Effects of cataract on peripapillary retinal nerve fibre layer and ganglion cell‐inner plexiform layer thickness measurement by cirrus optical coherence tomography
Authors: Park Chanjoon
Published: January 2024

Aims/Purpose: To assess the effect of cataract on peripapillary retinal nerve fibre layer (pRNFL) thickness and macular ganglion cell‐inner plexiform layer (mGC‐IPL) thickness measured by Cirrus (Carl Zeiss Meditec, Dublin, California, USA) spectral domain–optical coherence tomography (OCT).

Methods: Cirrus OCT was used to measure the pRNFL thickness and mGC‐IPL thickness in 44 patients (63 eyes) patients with cataract, including 43 glaucoma eyes. Cataracts were graded according to the Lens Opacities Classification System III. The study aimed to identify factors that could contribute to segmentation errors and variations in the signal strength index (SSI) or average thickness of mGC‐IPL and pRNFL.

Results: The prevalence of preoperative segmentation error were higher in pRNFL measurements compared with mGC‐IPL measurements (36.5% vs. 19.0%, p = 0.046). Multivariate analysis showed that segmentation error in RNFL measurements was significantly associated with preoperative SSI. Multivariate analysis indicated that preoperative SSI was highly correlated with changes with average thickness changes of mGC‐IPL and pRNFL.

Conclusions: Among eyes with cataract, the occurrence of segmentation errors was more common in measurements of the pRNFL compared to measurements of mGC‐IPL. Following cataract surgery, there was a slight increase in all thickness parameters in both mGC‐IPL and pRNFL measurements, although the differences were not statistically significant (p = 0.102 and p = 0.151, respectively). It is important to identify segmentation errors, particularly in pRNFL measurements of eyes with cataract and low SSI.
RNA‐binding protein ELAVL1‐mediated neuroprotection of retinal ganglion cells
Authors: Pacwa Anna , Machowicz Joanna , Rodak Piotr , Liu Xiaonan , Amadio Marialaura , Lewin‐Kowalik Joanna , Smedowski Adrian
Published: January 2024

Aims/Purpose: To evaluate the impact of ELAVL1 overexpression on survival and function of retinal ganglion cells (RGC) in rat glaucoma model.

Methods: The study included ex vivo and in vivo approaches. Ex vivo, we used rat retinal explants to investigate, whether AAV‐ELAVL1 delivery affects the survival of RGC in the degeneration model induced by axotomy. In vivo approach investigated histology and function of RGC in rat glaucoma model. Rats received intravitreal injection of AAV‐ELAVL1, AAV‐ELAVL1(S202A) or AAV‐control. To induce chronic glaucoma, unilateral episcleral vein cauterization was performed. Animals underwent electroretinography tests (ERG) during the experiment. Collected retinas and optic nerves were processed for immunostainings, western blots, and stereology.

Results: In ex vivo retinal explants culture, the RGC count was 162 ± 35, 148 ± 22 and 149 ± 28 for AAV‐ELAVL1, AAV‐ELAVL1(S202A) and control, respectively (p < 0.03). The IOP values were similar in all experimental groups, and on average, they were significantly higher than in healthy eyes (p < 0.001). In retinal histology, clear neuroprotective effect in the AAV‐ELAVL1 group was observed. After AAV therapy, both constructs (ELAVL1 and ELAVL1(S202A) showed a significant increase in protein expression in RGC, which was also associated with a significant increase in the expression of BDNF in the retinas, especially after AAV‐ELAVL1 treatment. In functional tests, the PhNR response was significantly reduced in AAV‐control glaucoma (p < 0.001). The application of AAV‐ELAVL1 treatment resulted in the preservation of RGC function at a level very similar to the situation before the induction of glaucoma.

Conclusions: The AAV‐ELAVL1 approach showed a very strong neuroprotective effect in a rat glaucoma model. The neuroprotective effect is associated with antioxidant and anti‐inflammatory activity with the increase in BDNF expression, which intensifies the neuroprotective effect.
Combined surgery and Preserflo coating with conjunctival graft autologous in acute pseudo‐exfoliative glaucoma
Authors: Ortega Aranzazu Caro , Prades Gemma Ortega , Pérez‐Torregrosa Vicente T. , Casado Francisco Calleja , Rovira Elena Gracia , Pérez Prudencia Rochina , Duch‐Samper Antonio M.
Published: January 2024

Aims/Purpose: To describe a case of cataract and acute pseudo‐exfoliative glaucoma in which combined surgery with a Preserflo implant was performed and required a conjunctival graft to cover the device due to the friability of the conjunctiva.

Methods: A 72‐year‐old male with glaucoma in the left eye (LE) with triple hypotensive treatment, who lost follow‐up due to the pandemic, goes to the emergencies for loss of vision in the LE. A medium dilation, pseudo‐exfoliation and white hypermature cataract can be seen. The intraocular pressure (IOP) is 45 mmHg and does not revert to adequate values with topical and systemic maximum hypotensive treatment. A temporary access cataract surgery is performed without complications. The glaucoma procedure is then performed using the Preserflo implant in the upper nasal area, but the suture produced buttonholes and tears in the conjunctiva that forced us to perform an autologous graft of inferior temporal conjunctiva to cover the implant and ensure a tight closure of the flap.

Results: The evolution of AV was favourable. IOP decreased to 10 mmHg and initially at biomicroscopy and Anterior segment optical coherence tomography (AS‐OCT) revealed a diffuse, functioning blister that progressively flattened. The graft was well adhered and positioned. The sclera of the donor area healed by secondary intention. At the 3‐month review, the device was vacuum packed and it was necessary to reintroduce hypotensive eye drops.

Conclusions: The Preserflo implant may be less traumatic than other filtering surgeries. The time with hypotensive eye drops contributes to the friability of the conjunctiva and makes us cover the device with an autograft to complete the surgery initially successfully. Although the chronic conjunctival damage may promote fibrosis, disrupt filtration, and require new hypotensive treatment.

References

1. Gambini G, Carlà MM, Giannuzzi F, Caporossi T, De Vico U, Savastano A, Baldascino A, Rizzo C, Kilian R, Caporossi A, Rizzo S. PreserFlo Microshunt: An Overview of This Minimally Invasive Device for Open‐Angle Glaucoma. Vision (Basel). 2022 Feb 9;6 (1):12.
Idebenone addition in protein‐loaded PLGA/VitE microspheres as neuroprotective IODDS
Authors: Morilla‐Lomeña Cristina , Reguera‐Insausti Blanca , Andrés‐Guerrero Vanessa , de la Torre Marta Vicario , Brugnera Marco , de las Heras Beatriz , Herrero‐Vanrell Rocio , Cuadrado‐Berrocal Irene , Bravo‐Osuna Irene
Published: January 2024

Purpose: Anti‐inflammatory and antioxidant evaluation of idebenone (IDB) in ARPE‐19 cell line and subsequent encapsulation in PLGA (polylactic‐co‐glycolic‐acid)/vitamin E microspheres (MS), together with neurotrophic factors, to confer additional neuroprotective activity and technological advantages.

Methods: ARPE‐19, a human RPE cell line, were incubated for 24 with IDB (0.5‐150 μM) to determine cell viability by MTT assay. For anti‐inflammatory evaluation, cells were pre‐treated with IDB (10 μM) for 3 h and then, stimulated with LPS (10 μg/mL;24 h). Interleukin‐6 (IL‐6) and chemokine CCL2 levels were quantified by ELISA. To determine the antioxidant activity of IDB, the induction of intracellular reactive oxygen species (ROS) was investigated. Cells were 3 h pre‐treated with IDB (10 μM), posterior exposed to hydrogen peroxide (H2O2) (100 μM;6 h), and measured by a Cellular ROS Assay kit. The elaboration of the PLGA/vit E MS loaded with IDB and protein was carried out by the method of extraction‐evaporation of the solvent from an S/O/W emulsion. Microspheres were characterized by SEM, Confocal microscopy and LDS. The protein encapsulation efficiency and the % released in the first 24 h of in vitro release study was measured by fluorimetry.

Results: IDB (10 μM) significantly suppressed LPS‐induced secretion of IL‐6 and CCL2 in ARPE‐19 cells. Moreover, pretreatment with the additive significantly attenuated the increased ROS levels in H2O2‐induced cells. Monodisperse spherical MSs were obtained with mean particle size suitable for intravitreal injection (29.41 ± 0.34 μm) and small superficial porous due to the presence of VitE. MSs showed a protein‐loading of 64.48 ± 1.99%. According to confocal images, protein was mainly distributed on the MS core. The initial protein release was 57.21 ± 10.89%.

Conclusions: The inclusion of IDB in the PLGA/VitE MSs loaded with active proteins could increase the neuroprotective activity of the IODDS as well as improve its technological characteristics.
Late T‐Flux extrusion: A series of 5 cases
Authors: Parot Álvaro Andrés Ojeda , Fabra Yolanda Cifre , Prades Gemma Ortega , Torregrosa Vicente Tomás Pérez , Pérez Prudencia Rochina , Samper Antonio Miguel Duch
Published: January 2024

Aims/Purpose: To Report T‐Flux® implant (Zeiss, La Rochelle, France) extrusion, as a new complication of non‐penetrating deep sclerectomy (NPDS). Analyse the risk factors that lead to it. Describe the treatment realized, and its complications.

Methods: 5 eyes of 5 patients who had undergone NPDS Surgery and presented a late T‐Flux® extrusion were included in this study. We made an epidemiological description of the cases. The treatment consisted in surgical exploration, extraction of the T‐Flux® and closure of the scleral and conjunctival defect. In 1 patient reopening of the scleral flap was needed to access and extract the implant. In the postoperative, values of intraocular pressure (IOP) and complications were evaluated.

Results: Of the 5 patients, 2 were man and 3 were female, the mean age was 78 years old, the mean time from the implantation until the extrusion was 11 years and 7 months. Mitomycin C was applied intraoperative during the NPDS in all cases, the concentration used was 0.02%, and the application time 1 min. 4 of the patients were operated by the same surgeon, one of the cases was re intervened later with trabeculectomy. All cases presented a partial or total dissolution of the scleral flap. There was no significant variation on the IOP prior and after surgery, The mean IOP at the diagnosis was 14 mmHg, and the mean IOP postoperative was 13.4. One patient had post surgical seidel that resolved without the need of re intervention.

Conclusions: Extrusion T‐Flux® implant is a late postoperative complication of NPDS, unknown up to date, that may occur many years after the original intervention. Treatment consists in surgical extraction and repair. In our experience this complication might be related to mitomycin C use, given that all of our eyes presented a scleral flap necrosis. There is a need of more reports on this complication, to approach its real incidence and predisposing factors.
Patterns of ganglion cell complex defects and association with functional status in glaucoma patients and suspects
Authors: Amorim‐Cabral Camila , Zangarini Vinicius , Pacovska Mayara , Hilariao Ana Aurea , Kasahara Niro
Published: January 2024

Aims/Purpose: To evaluate the frequency and patterns of ganglion cell complex (GCC) defects by spectral‐domain, high‐resolution optical coherence tomography (OCT) in POAG patients and suspects. Secondary endpoint was to analyse and compare the peripapillary retinal nerve fibre layer (RNFL) and GCC thickness as well as the visual field parameters among each GCC defect pattern.

Methods: This was a cross‐sectional study and included 220 patients with POAG and suspects. The OCT printouts were analysed by two examiners who carefully searched for GCC defects and in common agreement stratified them into 10 different patterns. GCC thickness, retinal nerve fibre layer (RNFL) thickness were determined for every participant from the exams; mean deviation (MD) and pattern standard deviation (PSD) values were retrieved from automated perimetry exams for every patient. The structural and functional variables were compared among the groups.

Results: The sample comprised 91 eyes of 47 patients. The most frequent GCC defect pattern was the minimal (39.1%). It affected more women than man at a rate of 1.4 and was associated with early disease (p < 0.001). The least frequent were inferior and superior confined (2.2% and 1.1% respectively); both were associated with moderate disease (MD = 10.0 dB, p < 0.001). The temporal raphe sign was observed in 5.5% of eyes and was associated with early disease (MD = −5.0 db).

Conclusions: In this cohort of Brazilians patients with POAG and suspects, the minimal pattern was the most prevalent GCC defect and was noticed in eyes with early disease. Clinicians should pay special attention to this defect when evaluation eyes with suspicious looking optic disc and POAG patients with early disease.
Peripapillary and macular vessel density changes after trabeculectomy
Authors: Jašinskienė Ernesta , Kadziauskiene Aiste , Asoklis Rimvydas , Schmetterer Leopold
Published: January 2024

Aims/Purpose: to evaluate peripapillary, optic disc and macular microvascular changes in glocomatous eyes after trabeculectomy using optical coherence tomography angiography (OCTA).

Methods: 90 eyes of 52 patients with primary open angle (20%), pseudoexfoliative (71%) and angle closure glaucoma (9%), and were included. 24 eyes (Group 1) underwent trabeculectomy during the study, 34 eyes (Group 2) had previous trabeculectomy three years more ago and 37 eyes (Group 3) had no trabeculectomy trabeculectomy. The AngioVue OCTA (Optovue Inc., Fremont, CA, USA) was performed at baseline (within one week before trabeculectomy for Group 1), one week and one month following baseline examination. The main outcomes of interest were changes in the superficial and deep macular vessel density (VD) as well as whole image and inside optic disc.

Results: The mean IOP at baseline was 25.3 ± 5.0 mmHg, 14.4 ± 3.7 mmHg and 14.7 ± 3.6 mmHg for the Group 1, Group 2 and Group 3 respectively. No significant differences in baseline characteristics were found between three groups, except for Group 3 group had milder glaucoma (it would be good to put the VF MD values of the groups). A reduction of IOP was observed in Group 1 one week and one month after trabeculectomy (14 ± 6.0 mmHg and 10 ± 6.2 mmHg respectively, p < 0.001). There were no significant IOP changes in Group 2 and 3. In all groups the changes in macular vessel density were nonsignificant. In Group 1 the mean inside disc small vessel density increased one week postoperatively (p = 0.04) and peripapillary vessel density increased one month postoperatively(p = 0.03) when compared with the baseline values. There was no significant difference in mean peripapillary or macular vessel densities between groups.

Conclusions: IOP reduction causes mild microvascular changes of optic disc and peripapillary regions in early postoperative period, however, does not affect macula.
Glaucoma screening: How and why?
Authors: Chafter Camilia , Maamouri Rym , Aoun Hichem , Nouri Hela , Meriem Ouederni , Cheour Monia
Published: January 2024

Purpose: To assess the results of glaucoma screening in the population over age 40.

Methods: A population‐based glaucoma screening was performed at Habib Thameur Hospital, Tunis TUNISIA on March 12, 2023. Screening included intraocular pressure (IOP) measurement with Goldmann applanation tonometry, visual acuity measurement (VA) with the Snellen chart, fundus examination to detect characteristic optic disc changes, and questions regarding systemic diseases, family history of glaucoma, and current medications.

Results: A total of 280 subjects were examined. Forty‐six had ocular hypertension, including 12 glaucomatous. All these patients were referred to the ophthalmology department for a complete ophthalmological examination, explorations (pachymetry, OCT of the optic nerve, visual field), treatment and regular follow‐up. Twenty‐two had unilateral or bilateral cataracts which we scheduled for surgery and fifteen had diabetic retinopathy at various stages which were referred to our specialist consultation for treatment.

Conclusions: The need for effective and early detection and management of glaucoma may reduce the prevalence of glaucoma‐induced blindness.
Liposomes versus microemulsions: Two novel nanosystems achieved an increased latanoprost hypotensive effect compared to traded medication
Authors: Brugnera Marco , Casamayor Miriam González‐Cela , Cano José López , de la Torre Marta Vicario , Guerrero Vanessa Andrés , Osuna Irene Bravo , Toral Fernando Huete , Rubio María González , Carracedo Gonzalo , Martínez Irene Molina , Vanrell Rocío Herrero
Published: January 2024

Aims/Purpose: The design of new topical ophthalmic nanosystems is linked to obtain non‐harmful carriers capable of increasing drug bioavailability and reduce the frequency of its instillations. Hypotensive actives such as latanoprost (L) are used to decrease intraocular pressure (IOP) in glaucoma patients. Two novel formulations, L‐loaded liposomes (LL) and L‐loaded microemulsions (LME), both including hyaluronic acid for its mucoadhesive properties were elaborated. The efficacy in reducing IOP of both formulations (48 h) was compared to a traded L‐ophthalmic solution (TM).

Methods: LL were manufactured by the lipid film hydration method using synthetic phospholipids and cholesterol. LME were produced according to the self‐emulsification method by employing well‐tolerated oils and co‐solvents. Both LL and LME were characterized in terms of pH, osmolarity, size distribution, viscosity, and surface tension. Their hypotensive effect was evaluated up to 48 h in normotensive male albino New Zealand rabbits (n = 6, 12 eyes) using a tonometer following a single 25 μL topical administration and related to TM (n = 6). Draize test was performed before and 4 h after the instillation to establish LL, LME and TM tolerance.

Results: Both LL and LME displayed proper physicochemical properties for the parameters evaluated. According to Draize test, both formulations resulted well‐tolerated without any sign of conjunctival hyperaemia, chemosis or discharge. Both LL and LME showed at least a 24‐h longer IOP reduction compared to TM, with the higher decrease at 3 h for LL and TM (24.02 ± 8.26% LL; 21.94 ± 10.14% TM) and 28 h for LME (30.40 ± 6.50%). Whilst at 24 h animals treated with TM (101.68 ± 5.27%) recuperated basal values, LL (91.08 ± 7.89%) and LME (80.14 ± 7.19%) rabbits still showed IOP decrease effect.

Conclusions: Liposomes and microemulsions showed a longer hypotensive effect compared to traded medication, which makes them encouraging novel compliance‐friendly eye drops for glaucoma treatment.

Acknowledgments: PID2020‐113281RB‐C21 funded by MCIN/AEI/10.13039/501100011033; 813440‐ORBITAL‐H2020‐MSCA‐ITN‐2018.
Study of the influence of care overburden on the indication for glaucoma surgery
Authors: Angulo Cristina García‐Velarde , Aroco Clara Lara , Blazquez Javier Guzmán , Martínez Teresa Pérez
Published: January 2024

Aims/Purpose: The indication for glaucoma surgery is a long process. Includes decision, information and administrative procedures. The purpose of the work is to study the factors different than the strictly clinical ones that condition the indication for surgery.

Methods: Retrospective study, consecutive sampling of glaucoma surgery indication with the variables age, sex, time of indication, number of patients attended per day and ratio indications/number of patients seen per day, type of glaucoma, type of surgery and physician who indicated it. The Shapiro–Wilk test was used to determine normality and the Kruskal‐Wallis test. The correlation between the ratio of surgeries and the total number of patients seen on the day (Sperman correlation) was measured.

Results: 131 surgeries were analysed, collected in 82 days of consultation during a year. The patients reviewed were 2886, of the annual total of 5255. The surgeries were indicated by 4 specialists and by residents. The mean age was 69.24 ± 13.49 years. The mean ratio of indication to the number of patients seen that day was 4.74% and the ratio to the total number of patients seen per year was 2.49%. The mean number of patients per day was 35.20 ± 13.20. The hourly distribution of the indications was: 3.1% between 8–9 h, 26% 9–10 h, 16% 10–11 h, 19.8% 11–12 h, 17.6% 12–13 h, 10.7% 13–14 h and 6.9% between 14–15 h. There were no significant differences in the ratio of indication per hour of indication (p = 0.318) or regarding the doctor (p = 0.295). There were significant differences between specialists with respect to the number of patients treated (p = 0.02). The correlation data were moderate and presented a statistically significant inverse relationship (p = −0.455), with a tendency towards fewer indications for glaucoma surgeries the more patients there are in consultation.

Conclusions: The care overload can influence the decisions when indicating glaucoma surgery.
Sigma‐1 receptor agonist ameliorates trabecular meshwork fibrosis by modulating extracellular matrix remodelling and increasing nitric oxide production
Authors: Hodrea Judit , Tran Minh , Besztercei Balazs , Medveczki Timea , Kovacs Illes , Gasull Xavier , Szabo Attila , Fekete Andrea
Published: January 2024

Purpose: Maintenance of normal tissue homeostasis in the trabecular meshwork (TM) is crucial for unaltered intraocular pressure (IOP). Fibrotic‐like disorder of TM can be one of the main causes of increased IOP. Thus, anti‐fibrotic drugs could be novel therapeutics for glaucoma. Nitric oxide (NO) has been recognized as an important regulator of TM outflow and maintain IOP. Recently, we reported that fluvoxamine (FLU), a potent sigma‐1 receptor (S1R) agonist, decreases the levels of key elements of fibrosis in the kidney and in lung. Therefore, here we investigated the antifibrotic effectiveness of FLU in mouse and human TM cells.

Methods: Fibrosis was induced with platelet‐derived growth factor (PDGF, 20 ng/mL, 24 h) in human and mouse primary TM cells (wild type: WT; and S1R knockout: KO). All cells were treated with 10 μM FLU for 24 h. Then localization of S1R, cell ‐toxicity, −proliferation and ‐migration, and levels of F‐actin, αSMA, fibronectin, and cathepsin K were determined with immunofluorescence or brightfield microscopy. NO production was measured with a fluorescent reader.

Results: S1R is localized in the endoplasmic reticulum and TM cells' cytoplasm. FLU treatment is non‐toxic and reduces the PDGF‐induced cell proliferation, migration and fibrotic protein levels (fibronectin, αSMA). Furthermore, in human TM cells, FLU increases NO production and the level of the protease, cathepsin K thus moderating the cytoskeletal rearrangements. The protective role of S1R in fibrosis is confirmed by the more prominent increase of αSMA and F‐actin bundle and clumps in the KO cells.

Conclusions: S1R agonist FLU reduces fibrosis‐related processes in TM cells by increasing NO production and facilitating ECM degradation. We propose in vivo investigations as a next step, since we believe that S1R activation could be a novel and efficient treatment in glaucoma or in other fibrosis related eye disease.

Grants

OTKA‐ K135398, LP2021‐3/2021, TKP2021‐EGA‐24.
EyeLife: A prospective glaucoma screening study with double‐blind genetic pre‐screening conducted within the population‐based Lifelines cohort
Authors: Jansonius Nomdo , Neustaeter Anna , Nolte Ilja , Snieder Harold
Published: January 2024

Purpose: Glaucoma screening potentially prevents blindness but is currently considered not cost effective due to insufficient screening test specificity given a low disease prevalence in the general population. Genetic pre‐screening could increase the prior probability (higher prevalence in a selected population). The aim of this study was to identify the relative risk of glaucoma in a subgroup of the general population with a high compared to one with a low genetic glaucoma risk.

Methods: The study protocol has been published previously (PMID: 33413217). We invited 1600 participants from the European Lifelines cohort (n = 165 000) aged 55+. Participants belonged to either the highest or lowest 20% of a GWAS‐based genetic risk score distribution; subgroups had similar age and gender. Researchers and participants were blinded regarding subgroup allocation. All participants underwent frequency doubling perimetry (FDT), optical coherence tomography (OCT) of the peripapillary retinal nerve fibre layer, and fundus photography to assess the optic nerve head (ONH). Any abnormal test result resulted in an ophthalmic exam including gonioscopy. Participants were classified as definite (abnormal FDT and either abnormal OCT or ONH), probable (either abnormal FDT or abnormal OCT and ONH), or possible (normal FDT with either abnormal OCT or ONH) open‐angle glaucoma (OAG), or as healthy. We obtained the relative risk of combined definite and probable OAG compared to healthy, excluding possible OAG.

Results: A total of 1031 participants responded (65%; 493 with high versus 538 with low risk). Of those, 31 (29 versus 2) were classified as definite and 28 (21 versus 7) as probable OAG. The prevalence of combined definite and probable OAG was 5.7%. The relative risk was 6.3 (95% CI 3.1–12.9).

Conclusions: Genetic pre‐screening seems a promising way to increase the prior probability of glaucoma and thus make glaucoma screening more cost‐effective.
External testing of an established glaucoma screening AI on a glaucoma clinic population from Finland
Authors: Hemelings Ruben , Schmetterer Leopold , Stalmans Ingeborg , Tuulonen Anja
Published: January 2024

Purpose: To assess the external performance of an existing deep learning regression model for glaucoma detection (G‐RISK) in a glaucoma clinic population from Finland.

Methods: Colour fundus images were retrospectively collected from the Tampere University Hospital (Tays), Finland. Eyes that had a visit in 2019 or 2020 were included based on the availability of ground truth labels. Ground truth labels for glaucoma were obtained through clinical evaluation of the optic nerve head (ONH) from colour fundus photos, clinical evaluation of retinal nerve fibre layer (RNFL) defects from fundus photos imaged with a cobalt filter, and clinical evaluation of the SITA Fast visual field (VF) test. Glaucoma diagnosis at Tays followed the ‘2 out of 3 rule’ recommended by the Finnish Evidence‐Based Guideline for Glaucoma, which requires at least 2 positive indications of glaucoma tests for referral [1]. Preprocessed colour fundus images were used as input to a previously trained deep learning model (G‐RISK) [2]. Performance was evaluated using the area under the receiver operating characteristic curve (AUC), accompanied by 95% confidence intervals. Patient aggregated results were obtained by comparing the maximum of both prediction and ground truth label.

Results: Over 3000 patients had at least one ground truth available for a visit in 2019 or 2020. Clinical evaluation of structural features (ONH, RNFL) triggered more glaucomatous symptoms than the SITA Fast VF test. When thresholding the AI prediction against a single ground truth type, the best AUC was obtained on the ONH label (0.90 [0.89–0.91]), followed by RNFL (0.84 [0.83–0.86]) and VF (0.83 [0.81–0.84]). When implementing the 2 out of 3 rule, AUC reached 0.88 [0.82–0.90].

Conclusion: The model performed best when using the ONH label and incorporating the ‘2 out of 3 rule’, reaching an AUC of 0.88. These findings suggest that the G‐RISK model could be a valuable tool for screening in clinical practice.

References

1. The Finnish Medical Society Duodecim. Update of Current Care Guideline for Glaucoma. March 28, 2023.

2. Hemelings, R., Elen, B., Barbosa‐Breda, J. et al. Deep learning on fundus images detects glaucoma beyond the optic disc. Sci Rep 11, 20 313 (2021).
Effects of primed adipose mesenchymal stem cell‐derived exosomes on immunomodulation in Behcet uveitis
Authors: Gözel Merve , Aydemir Ayse Dilara , Kaleli Humeyra Nur , Canbulat Zehra , Güleser Ümit Yaşar , Kesim Cem , Kızılok Billur Sezgin , Sahin Afsun , Uçar Didar , Hatemi Gülen , Hasanreisoğlu Murat
Published: January 2024

Aims/Purpose: Exosomes of interferon‐gamma (IFN‐ γ) primed (IFN + Exo) and non‐primed (IFN‐Exo) adipose‐derived mesenchymal stem cells (AdMSCs) were studied for their possible significance in the therapy of Behçet Disease (BD) uveitis (BU).

Methods: Adipose tissue was used to isolate AdMSCs. Characterization as well as multipotency investigations were carried out. Exosomes of AdMSCs were also identified and characterized. Lymphocytes were isolated from the peripheral venous blood of patients with BD uveitis (n = 15) and healthy controls (n = 15). AdMSCs were preincubated for 48 h with or without IFN‐ γ. Peripheral Blood Mononuclear Cells (PBMC) of BD uveitis patients and healthy controls were cultivated with exosomes separately for 72 h. Flow cytometry was used to assess lymphocyte proliferation, viability, and apoptosis after the culture period. Real‐time polymerase chain reaction (RT‐PCR) was used to assess the expression of interleukin‐10 (IL‐10), interleukin‐17 (IL‐17), transforming growth factor‐ β (TGF‐ β), and interferon‐ γ (IFN‐ γ).

Results: In patients with BD uveitis, IFN + Exo inhibited lymphocyte apoptosis. IFN + Exo reduced the viability of BD uveitis T lymphocytes. Both exosomes also raised IL‐10 level as an anti‐inflammatory cytokine and decreased IL‐17, TGF‐ β, IFN‐γ levels as a pro‐inflammatory cytokine in BD uveitis patients' lymphocytes. However, exosomes were ineffective in stimulating T lymphocyte proliferation.

Conclusions: Exosomes of AdMSCs stimulated with and without IFN‐ γ decrease the abnormal inflammatory response caused by BD uveitis PBMC. This study's findings have the potential to pave the road for MSC/exosome therapy in BD uveitis.