bluuebunny/crossref_metadata_2025 huggingface dataset:
Myopic maculopathy and posterior staphyloma. Correlation with ATN classification and severe pathological myopia
Authors: Garcia‐Zamora Maria , Flores‐Moreno Ignacio , Ruiz‐Medrano Jorge , Puertas Mariluz , Almazan‐Alonso Elena , Vega‐Gonzalez Rocio , Ruiz‐Moreno Jose M.
Published: December 2022

Purpose: The aims of this study were: (1) to correlate posterior staphyloma with the ATN classification; (2) identify differences in clinical characteristics in terms of axial length (AL), age and best corrected visual acuity (BCVA) in eyes with the presence and absence of posterior staphyloma; (3) correlate the presence of posterior staphyloma with severe pathological myopia.

Methods: This was a cross‐sectional and observational study developed in consecutive patients with high myopia. A complete ophthalmological examination, classification of myopic maculopathy according to the ATN grading system, staphyloma classification according to Curtin, and multimodal imaging tests (retinography, swept‐source OCT, autofluorescence and OCT‐angiography) were performed.

Results: 336 eyes of 178 patients with high myopia were included. 71.4% of the sample were woman. The mean AL was 29.7 ± 2.6 mm (26–36.7). The mean age was 62.7 ± 13.1 years (27–92). The BCVA was 0.5 ± 0.3 (0–1). 238 eyes (70.8%) presented staphyloma; classifying 73.5% (n = 175/238) as simple and 26.5% as compound (n = 63/238). The most frequent types of staphylomas were type 2 and type 3, both present in 18.1% of the total (n = 43/238). Eyes with staphyloma had higher AL, worse BCVA and older age (p < 0.01), with no differences between sexes (p > 0.05). When differentiating between eyes with simple staphyloma and compound staphyloma, statistically significant differences were observed with respect to AL (p < 0.01), being higher in compound staphylomas. The severe pathological myopia subgroup (LA > 29.5 mm) presented a higher incidence of posterior staphyloma, with statistically significant differences (p < 0.01). Regarding the ATN classification, when analysing the eyes with the presence and absence of staphyloma, statistically significant differences (p < 0.01) were observed in the three components (atrophic [A], tractional [T] and neovascular [N]); having more advanced stages of A, T and N the eyes with staphyloma.

Conclusions: Posterior staphyloma in highly myopic patients is a crucial finding in the progression of myopic maculopathy, being related to worse visual acuity, greater AL, older age and more advanced stages of the ATN classification. There is a higher prevalence of posterior staphyloma in eyes with severe pathological myopia.
Multilayered premacular haemorrhage associated with central retinal vein occlusion
Authors: Cherif Faten , Meriem Ouederni , Zaienb Gharbi , Fehmy Nafaa , Cheour Monia
Published: December 2022

Purpose: We aimed to report a rare case of multilayered premacular haemorrhage complicating central retinal.

vein occlusion (CRVO) and to describe its management and follow‐up.

Methods: An observational case report of a 38‐year‐old man with no medical history who presented with sudden loss of vision in his left eye (LE) 4 days ago. The patient underwent complete ophthalmologic examination, fluorescein angiography (FA) and swept‐source optical coherence tomography (SS‐OCT).

Results: Ophthalmologic examination of the right eye (RE) was unremarkable with a best‐corrected visual acuity (BCVA) of 20/20. In the LE, BCVA was limited to light perception (LP), intraocular pressure was 12 mmHg and anterior segment showed no abnormalities. Ophthalmoscopy showed dilated veins, multiple flame haemorrhages and a large dome‐shaped premacular haemorrhage with a double‐ring sign. SS‐OCT revealed a dome shaped clotted haemorrhage surrounded by hyperreflective dots under the internal limiting membrane (ILM) corresponding to a multilayered sub‐ILM haemorrhage. On FA, we noticed a delay in venous filling time and no areas of capillary‐non perfusion. Systemic work‐up with glaucoma screening were unremarkable. Nd:YAG laser hyaloidotomy and membranotomy of the ILM were performed. At one‐week follow‐up, there was evidence of the sub‐ILM and subhyaloid blood draining into the vitreous cavity. At 3 weeks following the laser treatment, persistence of clotted blood was noted. Pars plana vitrectomy with ILM peeling were performed. Two months post‐operatively, BCVA improved from LP to 20/25 with complete resolution of the haemorrhages on fundoscopy and SS‐OCT.

Conclusions: Premacular haemorrhage associated with CRVO is a rare condition. SS‐OCT allows accurate diagnosis and non‐invasive follow‐up. Nd: YAG laser hyaloidotomy should be considered as the first line treatment. But if failed, vitrectomy with ILM peeling should not be delayed in order to avoid toxic damages to the retina.
Effects of contact lens wearing on corneal sensitivity and reflex functions
Authors: Pastor‐Zaplana José Ángel , Gallar Juana , Acosta M. Carmen
Published: December 2022

Purpose: To study the effects of contact lens (CL) use on corneal sensory nerve activity, exploring corneal sensitivity and ocular functions regulated by sensory input in asymptomatic (CL‐A) and symptomatic (CL‐S) CL wearers.

Methods: CL wearers (23.8 ± 1.0 years; n = 31) participating in the study were classified as CL‐S when OSDI ≥13. Sex and age eye glasses (EG) users (24.5 ± 0.8 years, n = 29) participated as control group. Corneal mechanical, chemical and cold sensitivity was explored using a gas esthesiometer and 4°C‐saline drops; intensity, irritation and cold components of the evoked sensation were measured with Visual Analogue Scales (VASs). Tear volume (with phenol red threads), tear stability (TBUT), basal blinking frequency (BF), ocular surface temperature (OST; by IR thermography) were also assessed.

Results: CL wearers scored higher irritation VAS values than EG wearers for mechanical (2.5 ± 0.5 vs. 1.4 ± 0.4 for 160 ml/min air flow, CL vs EG, p = 0.09) and chemical stimuli (1.8 ± 0.5 vs. 0.7 ± 0.3 for 40% CO2, p < 0.05), and lower intensity values for cold stimulation (2.2 ± 0.4 vs. 4.5 ± 0.7, p < 0.05); tear volume was similar (27.0 ± 2.2 vs. 27.2 ± 1.6 mm), TBUT lower (8.3 ± 0.5 vs. 11.7 ± 0.5 s, p < 0.001), BF was higher (25.1 ± 2.4 vs. 14.3 ± 1.9 blinks/min, p < 0.001), and OST was lower (34.4 ± 0.2 vs. 35.2 ± 0.2°C, p < 0.01). VAS values for cold stimulation was slightly lower in CL‐S than in CL‐A (2.0 ± 0.4 vs. 4.0 ± 0.8, p = 0.06), while OST was higher (35.0 ± 0.2 vs. 33.9 ± 0.3°C, p < 0.01).

Conclusions: CL wearing affects corneal sensory nerve functions, changing corneal sensitivity, blinking rate, tearing stability, and OST. The changes found in corneal sensitivity fully agree with those described in neural activity of corneal sensory nerves after injury or inflammation using animal models: sensitization of corneal nociceptors and inhibition of cold thermoreceptors. The differences between CL‐S and CL‐A wearers could be due to the presence of subclinical ocular surface inflammation in symptomatic subjects.
Correlation between inflammatory profile in aqueous humour in patients who underwent cataract surgery using two techniques and cataract degree
Authors: Iranzo Guillermo Rodríguez , López Ester Fernández , Revert María José Roig , Martínez Cristina Peris
Published: December 2022

Purpose: Cataract surgery is one of the most usual type of intervention worldwide. Thanks to the improvement of technology and investigation this kind of surgery has reached a very high success rate. Studies have compared laser and conventional techniques in terms of inflammation, but there are also other variables which can influence the final result, such as cataract degree, age or diabetes. The purpose of this study is to establish the influence of cataract degree in the inflammatory profile of the aqueous humour.

Methods: The parameters determined in aqueous humour to compare both groups were interleukins (IL) 6 and 8 and cytokine tumour necrosis factor α (TNFα). Samples of aqueous humour were obtained during cataract surgery, before the lens was extracted and were analysed through Enzyme‐Linked Immunosorbent Assay (ELISA). Two study groups were established: femtosecond group (75 samples of aqueous humour from 75 patients) and manual group (54 samples of aqueous humour from 54 patients). Once this classification was made, the non‐parametric statistics of the median, Kolmogorov–Smirnov and the Mann–Whitney test were calculated to verify whether the degree of cataract influenced the inflammatory profile of aqueous humour.

Results: No significative differences were noticed between the two types of cataract degrees, early and advanced and their inflammatory reaction to surgery, although there is a slight tendency in IL6 and IL8 to increase their concentrations in advanced cataracts. On the other hand, the opposite happens with the concentration of TNFα that diminishes in advanced cataracts.

Conclusions: The inflammatory profile of aqueous humour can be affected by the type of surgery performed (femtosecond or manual surgery) but also by other variables such as age, diabetes or cataract degree. Regarding the last one, cataract itself can modulate ocular inflammation as there was a tendency in IL6 and IL8 to increase in advanced cataracts. Besides that, the decrease in TNFα aqueous humour concentrations in advanced cataracts may be due to a physiological attempt to restore basal cytokine levels.
Re‐audit of the preoperative, intraoperative and postoperative management of patients with diabetes undergoing cataract surgery within the National Health Services (NHS), United Kingdom (UK)
Authors: Mak Sammie , Jain Arpita
Published: December 2022

Purpose: Diabetes is a known risk factor of cataracts1. Diabetic patients are at an increased risk of macular oedema post‐cataract surgery, which can lead to poorer visual outcomes1. 9 months ago, an audit was conducted on the management of diabetic patients undergoing cataract surgery at Rochdale Eye Unit, United Kingdom. Recommendations following this included fundus examination with optical coherence tomography (OCT) scan to be part of preoperative assessment for this set of patients. Intraoperative steroid injections and postoperative topical non‐steroidal anti‐inflammatory drugs (NSAID) should be given as a standard, to reduce the incidence of diabetic macular oedema (DMO). A re‐audit aimed to assess implementation of changes in this subgroup of patients to standardize care and minimize risk of complications.

Methods: A retrospective analysis of 45 cataract surgeries performed in diabetic patients between January to April 2022 was conducted. Electronic records and Heidelberg OCT macula scans were accessed.

Results: 23 out of 45 patients (51.1%) had preoperative OCT, compared to 34.8% in cycle 1. No useful information could be obtained on pre‐ and postoperative OCT as few patients (13.3%) had both, which was the case in cycle 1 (17.4%). Out of 45 patients, 4 (8.9%) had intraoperative steroids given, reduced from 22% in cycle 1, and 35 (77.9%) received postoperative NSAID eyedrops, which was comparable to cycle 1 (78%). Eight patients (17.8%) had postoperative OCT, compared to 22% in cycle 1.

Conclusions: This 2nd cycle of the audit demonstrated an improvement in preoperative assessment of the macula and consistency in prescription of postoperative NSAID to diabetic patients undergoing cataract surgery. There has been a reduction in both use of intraoperative steroids and postoperative assessment of the macula. In order to implement the recommendations more effectively for the use of periocular steroid injections, stricter and more robust protocols will be discussed within the department and a short re‐audit planned within the next 3 months.

Reference

1. Zhang R, Dong L, Yang Q, Liu Y, Li H, Zhou W et al. Prophylactic interventions for preventing macular edema after cataract surgery in patients with diabetes: A Bayesian network meta‐analysis of randomized controlled trials. eClinicalMedicine. 2022;49:101463.
Clinical features and multimodal imaging findings in primary vitreoretinal lymphoma
Authors: Cherif Faten , Nesrine Abroug , Yassine Belguith , Mohamed Jeribi , Attia Sonia , Khairallah Moncef
Published: December 2022

Purpose: To describe clinical features and multimodal imaging findings in primary vitreoretinal lymphoma (PVRL).

Methods: Medical records and imaging findings of 4 patients (4 eyes) diagnosed with PVRL were retrospectively reviewed. Detailed ophthalmic examination, fundus photography, fundus autofluorescence (FAF), fluorescein angiography (FA), optical coherence tomography (OCT) and OCT angiography (OCTA) were analysed in all patients. All patients underwent vitreous biopsy for diagnosis confirmation. Brain magnetic resonance imaging (MRI) was performed in all cases.

Results: There were 2 women and 2 male patients with a mean age of 68.75 years. Visual blurring was the presenting symptom in all patients (100%). Clinical findings at presentation included vitritis in 4 eyes (100%), vitreous clumps in 2 eyes (50%), subretinal deposits in 3 eyes (75%) and exudative retinal detachment in one eye (25%). FAF showed granular hyperautofluorescence and hypoautofluorescence lesions in 3 eyes (75%) and blockage by mass lesion was seen in 1 eye. The most common pattern on FA was hypofluorescent lesions with a “leopard spot” appearance (75%). OCT revealed hyperreflective sub retinal lesions between retinal pigment epithelium and Bruch's membrane with an undulating shape (seasick sign) in 3 eyes (75%) and epiretinal membrane in one eye. OCTA showed areas of decreased signal on choriocapillaris slab in 2 eyes (50%). MRI of the globes and brain showed no abnormality in all cases. Vitreous cytology revealed atypical mononuclear cells consisting with the diagnosis of PVRL in all cases. The patients were referred to oncology unit.

Conclusions: The diagnosis of PVRL is challenging. Multimodal imaging provides novel insights into features of PVRL.
Histopathological findings of anterior lens capsule in paediatric cataract patients
Authors: Kızıltunç Pınar Bingöl , Özer Ferhad , İnanç İrem , Can Belgin , Atilla Huban
Published: December 2022

Purpose: To investigate the histopathological findings of the anterior lens capsule in patients with paediatric cataracts.

Methods: This study is a prospective interventional study. Anterior capsule tissue samples which were obtained by anterior capsulotomy method during phaco surgery were fixed in 0.1 M phosphate buffered 2.5% glutaraldehyde at +4°C for 2–4 h and after passing through other stages, thin sections were taken and stained. It was then examined and visualized under HITACHI HT7800 transmission electron microscope.

Results: Twenty‐three eyes of 19 patients were included. Three patients had unilateral cataract and remaining 16 had bilateral cataract. Four patients had concomitant systemic disease including hydrocephalus, cerebral palsy, juvenile myelomonocytic leukaemia and Down syndrome. Except for one patient, common findings were single‐layered epithelium under the capsule, degenerated organelles with round‐oval and prismatic‐oval nuclei in some regions, enlarged mitochondria and heterochromatin cells. In the case with cerebral palsy, unlike the normal lens structure, collagen fibrils of the connective tissue and fibroblast‐like cells were observed in the epithelial area that should be located under the capsule, in both eyes. Disorganized distribution of collagen fibrils and vacuole structures in the cytoplasm of fibroblast‐like cells were observed.

Conclusions: Similar histopathological findings were found in paediatric cataracts with or without systemic disease. Due to the presence of increased inflammation and gliosis in cerebral palsy, the absence of lens epithelium may have developed as a result of degeneration in this patient. The absence of lens epithelium and inflammation are thought to play a role in the development of dense subcapsular fibrosis.
Studies on intraocular transplantation of pancreatic cells in a large‐eyed preclinical animal model
Authors: Melin Yesenia Ortega , van Krieken Pim , Dicker Andrea , Berggren Per‐Olof , Kvanta Anders , Andre Helder
Published: December 2022

Purpose: Pancreatic islet transplantation (PIT) to the anterior chamber of the eye (ACE) has been shown to correct hyperglycemia and restore/improve glycemic control in rodents and non‐human primates. These studies also suggested that the eye may be in several ways a superior host site compared to the conventional hepatic portal system. In order to bring this technology to the clinic, it is essential to establish a large‐eyed non‐primate transplantation model. This proposal aims at establishing a rabbit ACE model of allogeneic PIT. We expect to gain insight into isolated islets function as well as ACE grafting efficiency and histological morphology in the large‐eyed rabbit model.

Methods: Pancreatic islets (PI) were isolated from Dutch Belted rabbits by injection of collagenase A into the pancreatic interstitium, digestion and hand picking under a stereo microscope. PI were cultured in RPMI medium overnight in a standard tissue culture incubator prior to assessment of purity. In vitro functional capacity of rabbit PI was assessed by glucose‐stimulated insulin release and intracellular Ca2+ imaging assays. PI were injected into the ACE an allogenic Dutch Belted rabbit using surgical procedures routinely applied in ophthalmology. PI engraftment and cellular content was analysed by anterior segment optical coherence tomography (ASOCT) and immunohistofluorescence (IHF).

Results: Isolated PI were of high purity with an approximate yield of 600–800 islets per pancreas. Preliminary results of functional capacity demonstrate that islets are responsive to high glucose stimulus, despite some variability. Allogeneic transplantation of isolated PI into the ACE of a Dutch Belted rabbit was followed by ASOCT. Engraftment was confirmed by IHF for vimentin. IHF suggests ACE engrafted islets are viable and maintain alpha, beta and delta cells.

Conclusions: The presented isolation method renders high purity and functional rabbit PI. Allogeneic transplantation of PI into the ACE was successful using clinically relevant procedures and resulted in islets engraftment and long‐term survival. These results may have implications for the clinical treatment of diabetes mellitus, particularly regarding patients with indications for PIT.
Preoperative noninvasive screening of dry eye in patients scheduled for cataract surgery
Authors: Vaccaro Sabrina , Scalzo Giovanna Carnovale , Rossi Costanza , Borselli Massimiliano , Mancini Alessandra , Lionetti Giovanna , Fratto Benedetta , Bianchi Pietro , Scalia Giovanni , Scorcia Vincenzo , Giannaccare Giuseppe
Published: December 2022

Purpose: To evaluate the rate of dry eye via noninvasive ocular surface screening in patients scheduled for senile cataract surgery.

Methods: Non‐invasive objective evaluation of ocular surface was performed in the eye undergoing cataract surgery by means of Keratograph 5 M (Oculus, Wetzlar, Germany) for the evaluation of: (i) tear menis‐cus height (TMH); (ii) non‐invasive break‐up time (NIBUT‐first). Subjective evaluation of ocular dis‐comfort symptoms was carried out by Ocular Surface Disease Index (OSDI) questionnaire.

Results: Thirty‐seven eyes of 37 patients (22 males and 15 females; mean age 73.68 ± 7.35 years) were ana‐lyzed. Of these, 28 eyes (75.67% of total) had altered values of NIBUT‐first and OSDI questionnaire (respectively 4.35 ± 2.74 s and 25.82 ± 17.29) but normal TMH values (0.40 ± 0.21); 4 eyes (10.81%) showed pathological values of OSDI score (35.75 ± 11.32) but normal values of TMH and NIBUT (respectively 0.46 ± 0.16 mm and 16.27 ± 5.33 s); 5 eyes (13.51%) had normal values of TMH, NIBUT and OSDI (respectively 0.48 ± 0.14, 11.28 ± 2.98, and 10.6 ± 3.13).

Conclusions: A fast and noninvasive screening of dry eye in patients undergoing cataract surgery showed that about three‐fourth of these patients had altered tear film stability and ocular discomfort symptoms. A prompt and customized treatment is needed in these patients preoperatively in order to optimize the surgical outcomes.
Macular choroidal thickness: A valid biomarker in multiple sclerosis patients
Authors: Ibáñez Marta Cerdà ‐ , Mora José Miguel Vilaplana , Domínguez Laura Manfreda , Duch‐Samper Antonio M.
Published: December 2022

Purpose: To analyse if there are retina microvascular changes and choroidal thickness changes correlate with the degree of disability among patients with sclerosis multiple (MS) disease during a year.

Methods: It was analysed the vascular changes (choroidal thickness and vascular macular plexuses) using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in multiple sclerosis (MS) according to the degree of disability measured by the expanded disability status scale (EDSS) in 1 year prospective study. Patients were divided into two groups: low disability group (EDSS score ≤ 3) and high disability group (EDSS > 3). Anatomical parameters and duration of the course disease was also analysed. Any subject has neuritis history and patients were divided depend on the type of MS: relapsing–remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS).

Results: Anatomical parameters were thinner in patients with the highest degree of disability and in patients with PPMS. Macular choroidal thickness (MCT) showed a significant decrease in the group which had moderate–severe disability. Retinal vascular macular plexuses showed no difference according to the EDSS score or type of MS.

Conclusions: Patients with a clinical worsening of their MS at 1 year showed a significant decrease in macular choroidal thickness compared to their baseline situation.
Psychometrics properties of a new scale to evaluate the impact of dry eye on daily life and the patient satisfaction using eye drops
Authors: Duracinsky Martin , Chassany Olivier , Gryparis Alexandros , Bodeveix Alice
Published: December 2022

Purpose: Dry eye disease (DED) impacts quality of life. Ocular Surface Disease Index (OSDI) and Dry Eye questionnaire (DEQ‐5) are 2 frequently used tools. OSDI is psychometrically sound but its 12 items do not cover all the patient experience. Validity of DEQ‐5 is questioned and the 1‐month recall period may introduce a memorization bias1. Aim of this study was to check the psychometrics properties of a new scale capturing a wider picture of patient perception.

Methods: Baseline data were from the TEARS cohort of 312 DED patients (Spain and UK) treated by a combination of sodium hyaluronate + trehalose. Apart of OSDI, DEQ‐5, and a global satisfaction, patients completed new questions (9 on impact of dry eye and 10 on satisfaction with eye drops) identified through a literature review and expert committee. These 19 items have a 4–5‐point Likert answers, and recall period is the last 3 days.

Results: Mean age of patients was 57.9 ± 15.2 years, 82.4% were women. Iterative factorial analyses were performed. 4 items were deleted (high inter‐item correlation, or no factor loading). A 4‐factor structure was found robust, ranked by their cumulative variance, and named by their content analysis: 1/DED impact on daily activities (n = 6); 2/perception of relief/being comfortable/duration with eye drops (n = 4); 3/DED impact on mood/sleep (n = 3); 4/easiness with eyes drops (n = 2). Reliability of the dimensions was confirmed by Cronbach alpha ranging from 0.67 to 0.86. Scores were calculated (range: 0–100 worst), e.g. 35.8 ± 20.6 for global score. Logical correlations between the 4 dimensions and OSDI, DEQ‐5 and global satisfaction ranged from 0.088 (Easiness vs OSDI) and 0.715 (impact on daily activities vs DEQ‐5). Correlation between global score versus OSDI was 0.440. 4 of the 5 DEQ‐5 items were highly inter‐correlated (>0.8) challenging its validity.

Conclusions: This 15‐item 4‐dimension scale has robust psychometrics properties. The next step is to quantify its responsiveness to change.

Reference

1. Okumura Y, Inomata T, Iwata N, Sung J, Fujimoto K, Fujio K, Midorikawa‐Inomata A, Miura M, Akasaki Y, Murakami A. A Review of Dry Eye Questionnaires: Measuring Patient‐Reported Outcomes and Health‐Related Quality of Life. Diagnostics (Basel). 2020;10(8):559.
Comparative analysis of posterior cornea between hydrops in keratoconus and Haab's striae in primary congenital glaucoma
Authors: Mahalingam Karthikeyan , Mandal Sohini , Singh Abhishek , Sen Seema , Titiyal Jeewan , Gupta Shikha , Gupta Viney
Published: December 2022

Purpose: More eyes with keratoconus (KC) require keratoplasty after hydrops when compared to those after haab striae in primary congenital glaucoma (PCG). To compare descemet's membrane (DM) tear morphology in KC and PCG eyes using ASOCT and histopathology.

Methods: ASOCT of KC eyes with hydrops (n = 12) and PCG eyes with Haab's striae (n = 15) were evaluated and compared with healthy eyes (n = 14) for descemet's membrane/ pre‐descemet's layer (DM‐PDL) morphology. These features were also assessed on histopathology of corneal button obtained from KC eyes (n = 14) and PCG (n = 13) after keratoplasty and compared with control tissues (retinoblastoma not involving cornea, n = 6) on light microscopy and immunostaining.

Results: ASOCT showed thinner DM‐PDL in KC eyes(47.1 ± 25.5 μ) than that of PCG (77.2 ± 26.2 μ) (p = 0.01) inside areas of healed hydrops/ Haab's striae. DM‐PDL detachment was seen in 90% of KC eyes and 26% of PCG eyes. The height and angle of DM‐PDL detachment of KC eyes was more than that of PCG eyes. Similar to ASOCT findings, histopathology showed thinner DM‐PDL in KC eyes (62.6 ± 57.3 μ) compared to PCG (80.3 ± 78.7 μ) inside areas of healed hydrops/ Haab's striae but thicker than that of controls (32.6 ± 7.8 μ) (p‐0.01).

Conclusions: Lesser fibroproliferative response and greater height of detachment ensure a poor healing after acute DM/ PDL tears in KC. This differential response of the posterior cornea may be responsible for greater need for keratoplasty in KC versus in PCG.
Ex vivo models of corneal epithelial regeneration in bioreactor: Respective roles of limbal, conjunctival and corneal epithelia
Authors: He Zhiguo , Perrache Chantal , Poinard Sylvain , Forest Fabien , Aouimeur Inès , Coulomb Louise , Moussa Olfa Ben , Vaitinadapoule Hanielle , Peyret Benjamin , Cortez Oliver Dorado , Sagnial Tomy , Mentek Marielle , Crouzet Emmanuel , Urbaniak Sébastien , Papillon Jean‐Marie , Maurin Corantin , Ninotta Sandrine , Mascarelli Frederic , Gain Philippe , Thuret Gilles
Published: December 2022

Purpose: The corneas preserved in bioreactor (BR) had been shown to have not only a better endothelial viability, but also a more differentiated and stratified epithelium than corneas preserved in organoculture. Purpose: By using BR, we would analyse the respective contribution of corneal (C), limbal (L), and conjunctival (Conj) epithelia in corneal epithelial regeneration.

Methods: Five pairs of corneas from body donation to Science were used with a death‐to‐collection time < 20 h. A 3‐ to 5‐mm‐wide conjunctival flange was kept intact. Five patterns were set up by fully mechanical removal of 1, 2, or 3 epithelia: C‐L + Conj+, C‐L‐Conj+, C‐L + Conj‐, C + L‐Conj‐, C‐L‐Conj‐ (control) n = 2 for each pattern. The limbus was destroyed by scraping and thermocoagulation. Corneas were then kept in BR (21 mmHg, 2.5 μl/min of Corneamax Eurobio, 31°C) for 3 weeks to allow epithelial regeneration. The epithelium was then analysed using immunofluorescence (IF) on flat mounted cornea by targeting CK12 (corneal epithelium) and CK15 (limbal epithelium). Cell nuclei were counterstained with DAPI. Corneal transparency was quantified using a transparometer.

Results: No epithelium was reconstituted in the controls. In the other 4 models including the C‐L‐Conj+ group, the cornea was transparent and covered by a pluristratified corneal epithelium, characterized by CK12 expression.

Conclusions: In this BR model, conjunctival epithelial cells allowed the regeneration of a typical corneal epithelium in model C‐L‐Conj+. The corneal epithelium can also migrate to the limbus and conjunctiva. We hypothesize that all 3 ocular surface epithelia (including the conj) contain stem cells or progenitors capable of migrating throughout the cornea and restoring the corneal epithelium independently of each other. The main difference between our ex vivo model and in vivo situation is absence of neovascularization. This suggests that the main cause of limbic insufficiency is due to the loss of the anti‐angiogenic barrier rather than the loss of limbic stem cells.
Adaptive optics scanning laser ophthalmoscopy characterization of cone photoreceptor reflectivity perturbation by drusen and subretinal drusenoid deposits
Authors: Zhang Yuhua , Wang Xiaolin , Liu Ruixue , Hoshi Sujin
Published: December 2022

Purpose: To examine the structure of photoreceptors around drusen and subretinal drusenoid deposits (SDD) in patients with age‐related macular degeneration (AMD) using multimodal imaging, including adaptive optics scanning laser ophthalmoscopy (AOSLO).

Methods: Thirty‐four (n = 34) patients with early to intermediate AMD were enrolled and classified into 3 groups based on predominant lesion type. Group 1 included 20 eyes of 15 subjects with medium‐large soft drusen (63–1000 μm diameter), group 2 had 15 eyes of 10 subjects with cuticular drusen (<63 μm), and group 3 had 14 eyes of 9 subjects with SDD. Lesion presence was ascertained by colour fundus photography, near‐infrared reflectance, blue reflectance, autofluorescence, and spectral‐domain optical coherence tomography (SD‐OCT). SDD were classified with a 3‐stage OCT‐based grading system. In addition, the reflectivity and packing mosaic of cone photoreceptors were assessed with AOSLO.

Results: AOSLO revealed characteristic photoreceptor reflectivity perturbation by different types of AMD's extracellular lesions. Around large soft drusen, the photoreceptor mosaic was invisible at the edge and visible on the top. The photoreceptors in the retinae with cuticular drusen were largely maintained as a contiguous mosaic but with reduced reflectivity over the lesions. Photoreceptors surrounding SDD showed reduced reflectivity associated with the SDD stage. The en face appearance of the photoreceptor mosaic was consistent with its cross‐sectional structure as rendered by SD‐OCT.

Conclusions: The dramatic photoreceptor reflectivity perturbation associated with SDD indicates that SDD may impose a more direct and severe impact on overlying photoreceptors than drusen, suggesting that the retinal function in eyes with SDD may be more severely impaired.@@@@
Generation and characterization of human USH2A retinal disease model
Authors: Flores Ana , García Belen , Garcia Gema , Mayordomo Noelia Pimentel , Gallardo Maria Esther , Garcia Carmen Ayuso , Millán Jose Maria , Lukovic Dunja
Published: December 2022

Purpose: Mutations in USH2A are the most common cause of autosomal recessive retinitis pigmentosa (RP) and syndromic RP in combined deaf‐blindness, Usher syndrome type 2 (USH2). In both cases, the effective treatment is lacking. The failure of retinal phenotype in available animal models warrants the generation of human tissue mimics in which to explore the underlying molecular mechanism and test available therapeutic modalities. To model this disease in vitro, we generated iPSC‐derived retinal organoids from the USH2 patient and isogenic control. We studied cellular and morphological alterations in retinal organoids and the effectiveness of gene editing to rescue retinal cell phenotypes. We describe the precise gene editing approach to genetically correct the p.Cys759Phe mutation in USH2A and hence generate the isogenic iPSC line.

Methods: The editing machinery was introduced by delivery of recombinant Cas9 and synthetic crRNA into the iPSCs derived from the patient bearing p.Cys759Phe mutation in USH2A. A single stranded oligonucleotide donor (ssODN) template carrying the wild‐type sequence was used to drive the mutation correction. The single cell clones were obtained and their edited genotype confirmed. Patient and isogenic control were subjected toward retinal organoid differentiation and analysed by fluorescence microscopy throughout the protocol, stage specific retinal cell markers were identified.

Results: The CRISPR/Cas9 gene editing approach generated homo‐and heterozygously corrected clones with acceptable efficiency. Patient and isogenic control lines were induced toward retinal organoids with all mayor retinal cell types. We observe reduced efficiency in neural retina formation and paucity in cellular laminar arrangement of patients' cells. The isogenic control was able to revert disease related cellular phenotypes and subcellular features.

Conclusions: Our study corroborates the feasibility of CRISPR/Cas9 editing of genetic lesion in monogenic disease bearing hiPSCs further supporting the applicability of CRISPR/Cas9 machinery in in vivo settings. We have identified retinal cell phenotype in USH2A p.Cys759Phe disease background which allows us to study disease mechanism and test novel treatment options.
Surgical management of disc pit maculopathy: A case report
Authors: Fernández Miguel Castillo , Rivasés Guilermo Pérez , El Bakkali Ismael Bakkali , Moscarda Eva Josefina Núñez , de Rivas Marta Orejudo , Arias Pablo Andrés Cisneros , Martínez Marta Suñer , Clavería Julia Aramburu , Floria María Olivia Esteban , Sesé Isabel Bartolomé , Puyuelo Javier Ascaso , Lozano Isabel Pinilla
Published: December 2022

Purpose: Optic disc pit (ODP) is a rare congenital disorder that affects one in 10 000 people. Serous detachment of macula is the most common complication and the natural history of untreated ODP maculopathy is a gradual deterioration with significant visual loss. A multitude of interventions have been designed for the treatment but none has been established as the treatment of choice. Pars plana vitrectomy is one of the most commonly used procedure in recent years. We present a case report with surgical treatment and management of complications.

Methods: An interventional case report of a 63‐year‐old man who attended the emergency room due to sudden visual loss and best corrected visual acuity (BCVA) of 20/200 in the right eye (RE). Upon his arrival, a visual field was performed in which complete abolition of the right field was observed, severely affecting the central area. A papillary pit was found in the eye fundus. Optical coherence tomography (OCT) revealed a serous retinal detachment (RD) with macular involvement and surgical management was decided.

Results: A successful pars plana vitrectomy (PPV) with peeling of the internal limiting membrane and application of an endolaser was performed. Three months later, he came back with a higher serous RD and a worsening of BCVA. We performed a second PPV with sulfur hexafluoride (SF6) with good anatomical results. One year later, cataract and an inferior rhegmatogenous retinal detachment with proliferative vitreoretinopathy (PVR) was treated with intraocular lens implantation and PPV with silicone oil. Five months later, supero‐temporal retina was detached, so a new PPV was carried out with silicone oil again. One year later, the silicone oil was removed and a retinal detachment was noted 3 months later. Finally, the last surgery was performed practicing encircling band, PPV, application of endolaser and again using silicone oil.

Conclusions: Surgical management of serous retinal detachment caused by papillary pit continues being a challenge for retinal specialists. Complications of surgery are no usually publish in literature and this case report make us take into account. Since it ranges from observation to surgical approach using different techniques and procedures without any showing clear superiority.
Administration of dutasteride in animal models of retinitis pigmentosa
Authors: Sanz María Miranda , Cantó Antolin , Olivar Teresa , López‐Pedrajas Rosa , Martínez‐González Javier , Hernández‐Rabaza Vicente , Almansa Inmaculada
Published: December 2022

Purpose: Retinitis pigmentosa (RP) describes a large group of hereditary retinopathies. It mainly affects the rods. However, once the rods have degenerated, the cones, also die, leading to complete blindness. Although, the mutations that cause RP have been identified in different genes, the mechanisms that cause the death of photoreceptor cells are still unknown. Gonadal hormones may play a protective role in RP. Our research group has shown that oral administration of progesterone to RP mice significantly conserves the number of photoreceptors. 5α‐reductase inhibitors (such as dutasteride (DUT)) are approved treatments for androgenic alopecia. Modulation or inhibition of 5α‐reductase activity increases the levels of the neuroprotective steroid progesterone and 17β‐estradiol. The purpose of this study was to administer DUT to RP mice. This may be another form of increasing progesterone levels in the retina and therefore, may be neuroprotective.

Methods: Animals were treated in accordance with the ARVO statement for the use of animals. rds mice were treated intraperitoneally with DUT and euthanized on day 21. Haematoxylin–eosin, cell death, and rod and cone immunohistochemistry were performed to determine if DUT was able to delay photoreceptor death. Immunohistochemical techniques were used to study changes in retinal microglia (Iba‐1) and macroglial cells. Neuronal nitric oxide synthase (nNOS) was also quantified.

Results: DUT increased photoreceptor survival in rds mice. An increase in iba‐1 positive cells was found in rds retinas and DUT normalized the number, migration and the length and number of branches in these cells. DUT decreased GFAP (glial fibrillar acid protein) expression. We have also observed a slightly increase in nNOS expression in rds mice. DUT administration was also able to decrease nNOS expression.

Conclusions: DUT may be used to improve cell survival, to ameliorate retinal micro and macroglial activation as well as alterations in nNOS in RP.
Changes in retinochoroidal vascularization evaluated by OCTA in long time evolution DM1 patients
Authors: Pinilla Isabel , Sopeña‐Pinilla Maria , Boned‐Murillo Ana , Díaz‐Barreda Mª. Dolores , Fernández‐Espinosa Guisela , Bartolome Isabel , Acha Javier , Hospital Elvira Orduna
Published: December 2022

Purpose: To study anatomical and vascular changes in the superficial capillary (SCP) and deep capillary (DCP) plexuses in the retina, as well as changes in the choriocapillaris (CC) and foveal avascular zone (FAZ) using optical coherence tomography angiography (OCTA) in type 1 diabetic (DM1) patients without diabetic retinopathy (DR).

Methods: We performed a single‐center cross‐sectional descriptive study including 68 eyes of well‐controlled DM1 patients who had been diagnosed at least 10 years prior, and 88 eyes of 88 healthy subjects. All participants underwent a full ophthalmic examination including OCTA using Deep Range Imaging (DRI)‐Triton swept source (SS)‐OCT.

Results: six eyes were excluded from the DM1 group after checking the quality of our measurements, resulting in a final sample of 62 eyes. Mean age was 43.79 ± 11.31 and 47.16 ± 15.48 years in the DM1 group and in the control group respectively. There were no differences in VA, EE, AL nor IOP. Statistically significant differences were found in all areas of the SCP, except for the central area, with lower values in DM1 patients. There were differences in all quadrants except the central zone and the superior quadrant in the DCP. In the CC, there were only significant blood flow changes in the central area. We did not find significant differences in the FAZ in neither of the plexuses, but the horizontal FAZ SCP diameter was found significantly different. The anatomical evaluation frequently showed abnormalities such as microaneurysms in both plexuses, FAZ modifications and areas with lack of blood perfusion.

Conclusions: Type 1 diabetic patients without DR present microvascular abnormalities with lack of retinal and CC blood perfusion, as well as anatomical changes in retinal blood vessels.
Long‐term follow up of macular perfusion evaluated by optical coherence tomography angiography after rhegmatogenous retinal detachment surgery
Authors: Pinilla Isabel , Bartolome Isabel , Díaz‐Barreda Mª. Dolores , Boned‐Murillo Ana , Fernández‐Espinosa Guisela , Sopeña‐Pinilla Maria , Hospital Elvira Orduna
Published: December 2022

Purpose: To investigate macular microvascular changes using OCTA in patients one‐year after a successful RDD surgery.

Methods: Cross‐sectional study including RRD treated using PPV ± SB and SF6 tamponade. Eyes were divided related to their macular status previous surgery and depending on the surgical technique used. All the subjects underwent complete ophthalmological examinations including a 3x3 OCTA protocol using DRI‐Triton swept source (SS)‐OCT with a minimum 12 months follow‐up after the surgery. Retinal capillary plexuses and CC vessel density (VD) were studied. FAZ area and diameters were measured. Results were compared with the unaffected contralateral eye.

Results: Sixty eyes of 57 patients with RRD were included. Mean age was 59.14 ± 9.52 years. PPV was performed in 68.3% of the eyes, associated to SB in 31.6%. The macula was affected in 38.3% of the eyes and unaffected in 61.7%. RRD macula‐off had lower VA than the contralateral eyes. No differences were observed in VD between RRD macula‐on eyes regardless of the surgical technique performed. However, one year after surgery, we observed a significantly increased VD in the central area of macula‐off RRD eyes treated with PPV + SB in both retinal plexuses and in the SCP of RRD treated with PPV compared to the fellow eyes. All the macula‐off treated eyes had a diminished VD for both SCP and DCP in the superior quadrant and in PPV + SB we also found a diminution in the inferior quadrant for the SCP. In the inferior quadrant, we only found a diminution in the SCP flow in macula‐off treated with PPV + SB. We found changes at the CC level in the temporal quadrant of the macular‐off treated with PPV + SB. We did not observe differences in FAZ area between any groups. FAZ horizontal and vertical diameters were statistically smaller in patients with macula‐off RRD.

Conclusion: Macular vascularity remains almost unchanged in patients one year after successful RRD surgery, despite the surgical technique (VPP vs VPP + SB). Vascular changes are not remarkable in neither macula‐on not macula‐off RDD. We found an increase in VD in the central area of the retinal capillary plexus in patients after macula‐off RDD associated to a diminution in VD of both superior and inferior quadrants of the retinal plexuses suggesting changes in vascularization after macula‐off RRD surgery.
Multimodal imaging in persistent fetal vasculature
Authors: Gouider Dhouha , Sayadi Jihene , Choura Racem , Raihan Haythem , Mekni Manel , Aidi Nourhene , Zeghal Imene , Malek Ines , Nacef Leila
Published: December 2022

Purpose: To describe the clinical manifestations of the persistence of the fetal vascular system and to show multimodal imaging findings in this disease.

Methods: We presented two cases of persistent fetal vasculature. Thorough clinical examination and full multimodal imaging have been undertaken.

Results: The first case is a 12‐year‐old girl who consulted for a visual impairment evolving for few years. Fundoscopy revealed a unilateral whitish vascular membrane attached to the optic disc towards the vitreous associated with retinal folds in interpapillomacular region as well as chorio‐retinal atrophy and nasal pigment migrations. B‐mode ultrasonography confirmed the presence of this membrane attached to the optic disc but does not reach the lens. Optical coherence tomography (OCT) showed a deficit of RNFL, especially in superotemporal and hyaloid condensation in the optic disc with macular folds. The second case is a 42‐year‐old patient who consulted for a presbyopia. Fundoscopy revealed membranous short band‐like lesion attached to the optic disc associated with retinal folds, better seen in the anerythral photograph which showed an alternation of grey and white bands.

Conclusions: Multimodal imaging is of a paramount importance in diagnosing the fetal vascular system. It also allows the recognition of the form of this disease and thus the way to manage it.
OMNI®, the new surgical option in the treatment of glaucoma
Authors: Merino Jacobo Yáñez , Hermosín Mario García , Rufas Ines Munuera , Navarro Damian Garcia , Merino Andres Biescas , Arenas Blanca Ferrández , Poves Jose Manuel Larrosa
Published: December 2022

Purpose: The mechanisms of elevation of intraocular pressure (IOP) in eyes with open‐angle glaucoma are complex and probably include problems related to alterations in the trabecular network, Schlemm channel and distal collecting channels. Traditional surgeries, such as trabeculectomy and the implantation of a shunt microtube, avoid these structures and divert the aqueous humour to the subconjunctival space. Recently, a growing family of minimally invasive glaucoma (MIGS) surgeries has evolved to achieve the reduction of IOP without blistering by restoring flow through the conventional physiological route of exit. One of the devices in this family is the OMNI® surgical system, which was designed to address the three sources of resistance to output flow: trabecular network, Schlemm channel and distal collectors. Thanks to this device it is possible to perform two procedures with a single surgery and overcome three points of flow resistance.

The relative novelty of this device makes it important to monitor and analyse long‐term results in normal clinical practice.

Methods: We present 6 clinical cases of chronic open‐angle glaucoma that were subjected to surgery with the OMNI® device, associating cataract phacoemulsification in 5 of them.

Results: The reduction in IOP that we have observed at 3 and 6 months is around 30%, which is very similar to what has been published in the literature.

Conclusions: In our experience, the OMNI® surgical system has provided a clinically relevant decrease in IOP and the number of active ingredients needed, with a good safety profile, although a greater volume of patients and follow‐up time are required to draw more precise conclusions.