bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrastructure of collagen fibrils, proteoglycans and lamellae of the human cornea treated with Iontophoresis ‐ UVA cross‐linking and hypotonic riboflavin solution
Authors: Akhtar Saeed , Almubrad Turki , Smedowski Adrian , Samivel Ramachandran , Almutleb Essam , Alkanaan Aljoharah , Khan Adnan , Masmali Ali , Mencucci Rita
Published: January 2022

Purpose

To investigate the effect of iontophoresis‐UVA cross‐linking with hypotonic riboflavin solution on the ultrastructural changes in the lamellae, collagen fibrils (CF) and proteoglycans (PGs) in the central and peripheral stroma of the human corneal buttons.

Methods

Iontophoresis method was used for the trans‐epithelial application of hypotonic riboflavin in ex vivo corneal culture for 5 minutes. The corneas were irradiated using three methods; Group 1 (G1): an UV‐A irradiance of 3 mW/cm2 for 30 minutes; Group 2 (G2): an UV‐A irradiance of 10 mW/cm2 for 9 minutes; Group 3 (G3): without UV‐A irradiation. Three untreated corneas were used as a control group (G0). After CXL procedure, the corneas were processed for electron microscopy. CF diameter and PGs in each sample were analyzed using iTEM program.

Results

The keratocyte organelles and stromal architecture in the peripheral cornea were better preserved than in the central cornea. The mean CF diameter in the peripheral cornea of the ‘G1 and G2’ was significantly higher compared to those in the central cornea. In G3, the central corneal CF diameter was significantly larger than the peripheral corneal CF diameter. There were also differences in the PGs area size between the central and peripheral cornea in all groups.

Conclusions

Riboflavin + UVA application at 3mW2 /cm for 30minutes and 10mW2/cm for 9 minutes is a suitable method of CXL; however, the 10mW2/cm for 9 minutes combination seems to present stronger phototoxic effect and better prognosis for corneal healing. CXL treatment was more effective at the periphery than center.

Acknowledgments

This research project was funded by National Plan for Science and Technology Program (Grant Number 15MED4229‐02), King Saud University.
Intraoperative 96% ethanol as an adjuvant in Pterygium (Pt) surgery
Authors: Gancedo Maria Luisa Perez , Reina Alfonso Rubio , Martin Laura Alonso , De Los Angeles Leal González Maria , Leon Maria Mercedes Cabezas , Vazquez Maria Platero , Diaz Oier Perez , Cardeñosa Nuria Cuenca , De Paz Sergio Pérez , Quiroz Nolvis Marina Alvarez , Lozano María Belén Morcillo , Rodríguez Beatriz González , Serrano Famara Doblado , Lopez Fernando Sellers , Silva Bruno Casco , García Maria Josefa Fernández , Carranza Maria Zulema Hernandez
Published: January 2022

Purpose

The aim of the study is to present how we use ethanol on the cornea next to the pterygium head to remove the corneal epithelium and create a dissection plane to remove the fibrovascular tissue in a more controlled way leaving a more regular corneal surface.

Methods

Topical tetracaine + oxybuprocaine as topical anaesthetic, povidone iodine 5% is instilled and mepivacaine 2% is injected under the body of the pterygium. A cellulose sponge soaked in 96% ethanol is placed over the corneal surface 1‐2 mm around the head of the fibrovascular tissue for 10 seconds, then washed. Blunt lifting of the epithelium towards the head of the pterygium allows identification of the surgical plane for dissection of the underlying corneal adhesions. Excision of the corneal encroaching tissue, tennon's capsule over the bare sclera and under the conjunctival wound was followed by conjunctival autograft sealed with fibrin (tisseel).

Results

A retrospective review of all pterygium procedures performed at our institution from January 2017 to January 2020 was performed to find out if there were any intra‐ or post‐surgical complications related to the use of 96% ethanol. All patients had completed epithelialisation within 1 week and none had limbal deficiency. The recurrence rate was very low.

Conclusions

Intrasurgical application of 96% ethanol on the cornea next to the pterygium head for 10 seconds just before surgical removal of the pterygium is an inexpensive, safe and effective adjuvant to the procedure. It may even be of more interest in recurrent pterygium where firm adhesions need to be addressed and creating a new smooth surface may prevent recurrences.

Bibliography

Kaufman SC, Jacobs DS, Lee WB, Deng SX, Rosenblatt MI, Shtein RM. Options and adjuvants in surgery for pterygium: a report by the American Academy of Ophthalmology. Ophthalmology. 2013 Jan;120(1):201‐8. https://doi.org/10.1016/j.ophtha.2012.06.066. Epub 2012 Oct 11. PMID: 23062647.

Chen KH, Hsu WM. Intraoperative ethanol treatment as an adjuvant therapy of pterygium excision. Int J Biomed Sci. 2006 Dec;2(4):414‐21. PMID: 23675010; PMCID: PMC3614651.

Tsumi E, Levy J, Pitchkhadze A, Baidousi A, Lifshitz T. New approach for pterygium removal using 20 % ethanol. Int Ophthalmol. 2012 Oct;32(5):443‐8. https://doi.org/10.1007/s10792‐012‐9597‐2. Epub 2012 Jun 21. PMID: 22717949.
Ocular surface squamous neoplasia (OSSN) in an 84‐year‐old female patient
Authors: Vera Luisa Fernanda , Gallarate Gabriella , Pagano Marco
Published: January 2022

Purpose

To report a case of Ocular Surface Squamous Neoplasia, in an 84 years old woman. The patient referred 4 months of red vascularized elevated corneal lesion.

Methods

Our proposal was an exportation of the conjunctival corneal neoformation and histological examination. During the surgical procedure, we found an elevated lesion with feeder vessels, the surgical excision biopsy was done and the specimen was sent for histopathological evaluation, which revealed an invasive, poorly differentiated carcinoma extending to subcutis. Immunohistochemical staining for p63 gave dubious results on the integrity of the basement membrane. These findings associated with the incomplete excision of the lesion did not allow us to express a possible invasiveness in the lateral margin affected.

Results

In the post‐operative, we used Mitomycin C 0.04% topical treatment, 4 times a day for a week, then 3 weeks off for a total of 3 cycles. During this period the patient did not display any adverse systemic or ocular reactions. At the end of the treatment, we found a complete regression of the disease. During the control at 6 months and 1 year, the patient was asymptomatic.

Conclusions

Diagnosis of invasive Squamous Cell Carcinoma mainly rests on the histopathological examination of the excised lesion. No serious ocular or systemic side effects were observed during the Mitomycin C 0.04% eye drops treatment. Mitomycin C 0.04% seems to be a safe and effective treatment for ocular surface squamous neoplasia.
The suppressive role of sex steroids in inflammatory response and viability of limbal mesenchymal stem cells under stress condition
Authors: Kuşan Eda , Zibandeh Noushin , Şahin Afsun
Published: January 2022

Purpose

To investigative the regulatory role of sex steroids on mitogen‐activated protein kinase pathway, autophagy pathway, and cell survival of Limbal Mesenchymal Stem Cells (LMSCs) under serum starvation induced stress conditions.

Methods

The L‐MSCs were isolated from cadaver corneal tissues and were characterized by flow cytometry and were differentiated into 3 lineages. The L‐MSCs in passage 3 were cultured with low glucose DMEM completed with fetal bovine serum (FBS) and penicillin‐streptomycin until reaching 80% confluency. After confluency, cells were trypsinized and cultured with charcoal FBS containing medium either with 10‐8 M dihydrotestosterone (DHT) or 10‐8 M 17‐β‐estradiol. After 48 hours, the medium was changed to only DMEM without any serum supplement for the purpose of serum starvation. Serum starvation treated cells for all conditions were lysed and western blot analysis was applied for phosphorylated forms of extracellular signal‐regulated kinase 1/2 (ERK1/2), p38 kinase, c‐Jun N‐terminal kinase 1/2 (JNK1/2) and as an autophagic marker, Beclin‐1 ATG‐7 and LC3I‐II. The LMSCs viability was measured with Annexin V/propidium iodide.

Results

P‐JNK and P‐ERK were inhibited only by 17‐β‐estradiol pretreated groups while pretreatment LMSCs with DHT and 17‐β‐estradiol suppressed the upregulation of p‐p38 up to 4 hours of serum starvation stress. The expression of Beclin‐1 was not significantly changed in both groups, while expression of ATG7 was significantly inhibited in the 17‐β‐estradiol group for up to 4 hours. The conversion of the LC3‐I to LC3‐II was found to be suppressed in both groups compared to the control group. DHT and 17‐β‐estradiol pretreated L‐MSCs were increased cell survival compared to untreated conditions.

Conclusion

According to our results, DHT and 17‐β‐estradiol especially 17‐β‐estradiol suppressed the mitogen‐activated protein kinase signalling pathway and autophagic pathway. These findings may help to explain the function of sex hormones in various ocular surface illnesses, as well as their implications for treatment.
IFNγ reduces viability in human conjunctival goblet cells in vitro
Authors: Rævdal Pernille , Nagstrup Anne Hedengran , Thyssen Jacob Pontoppidan , Heegaard Steffen , Kolko Miriam
Published: January 2022

Purpose

Conjunctival goblets cells play an important role in the homeostasis of the ocular surface and are known to be affected by inflammatory cytokines in diseases of the ocular surface. An understanding of the role of interleukin (IL)‐4, IL‐13, IL‐17, and interferon (IFN)γ in conjunctival goblet cell survival and function is necessary to explore the pathogenesis of ocular surface diseases. Previous studies have shown that IFNγ reduces the survival of the goblet cells, whereas IL‐13, IL‐4 and IL‐17A induce proliferation in mouse and rat models (1). The purpose of this study was to investigate the effect of IL‐4, IL‐13, IL‐17A and IFNγ on human goblet cell survival assessed by LDH analysis.

Methods

Human goblet cell cultures were grown from cultured donor conjunctiva. The goblet cells were seeded into wells and stimulated with IL‐4, IL‐13, IL‐17A and IFNγ with 100 ng/mL for 48 hours, respectively. Cell viability was evaluated by LDH assays.

Results

Stimulation with IFNγ showed significant decrease in goblet cell viability with LDH assay (p<0.01). Stimulation with IL‐4, IL‐13 and IL‐17A showed no significant decrease in cell survival compared to control. Significant differences in cell survival were observed between stimulation with IFNγ and IL‐4 (p<0.001) and IL‐13 (p<0.05), respectively.

Conclusions

Our study indicates that IFNγ reduces human conjunctival goblet cell survival in contrast to the Th2‐associated cytokines IL‐4 and IL‐13.

Reference

García‐Posadas L, Contreras‐Ruiz L, Soriano‐Romaní L, Dartt DA, Diebold Y. Conjunctival Goblet Cell Function: Effect of Contact Lens Wear and Cytokines. Eye Contact Lens 2016;42(2): 83–90.

Conflict of Interest

This work was supported by a research grant from LEO Pharma.
Importance of monitoring the ocular surface of patients with Kearns‐Sayre syndrome: a case report
Authors: Rivasés Guillermo Pérez , Diaz Barreda Maria Dolores , Murillo Ana Boned , El Bakkali Ismael Bakkali , De Rivas Marta Orejudo , Moscarda Eva Josefina Nuñez , Arias Pablo Cisneros , Puyuelo Javier Ascaso , Alvarez Constanza Maria Caramello
Published: January 2022

Purpose

Kearns‐Sayre Syndrome (KSS) is a congenital mitochondrial myopathy initially described by the triad: Progressive external ophthalmoplegia, pigmentary retinopathy, heart block. Surgical procedures to alleviate ptosis can cause corneal injury from exposure. The lack of blinking can lead to a difficult contraction of the muscles responsible for squeezing the meibomian glands causing their dysfunction (MGD). Therefore, the follow‐up is of special interest in those cases where we suspect KSS due to the probable appearance of complications.

Methods

We present the case of a male of 9 years old who presented a sudden‐onset ptosis and bilateral internuclear ophthalmoplegia. Initially, he was diagnosed with Myasthenia. At the age of 12, resection of the elevator upper eyelid was performed in both eyes (BE). In the successive visits: negative Bell's sign, a progressive MGD and significant corneal thinning in the lower half of the BE were observed, and the right eye (RE) was affected with an infiltrated ulcer.

Results

Treatment with high hydration in BE and RE was treated with antibiotics eye drops and antibiotic ophthalmic ointment. After reviewing the history and given the high suspicion of KSS, genetic tests were requested to confirm it. Maintenance treatment was settled in BE with high hydration, 20% autologous serum and therapeutic contact lens. After a year of exhaustive monthly follow‐up, the patient remains stable and there is no progression of the corneal thinning.

Conclusions

It is important to take care of the ocular surface in these cases of KSS due to the corneal exposure after ptosis surgery. We must achieve stability in terms of symptoms and visual acuity without incurring other complications such as infections or perforation.
Descemet’s membrane rupture due to forceps injury: macroscopic aspect by anterior segment optical coherence tomography
Authors: El Bakkali Ismael Bakkali , Arias Pablo Cisneros , Rivasés Guillermo Pérez , Murillo Ana Boned , Barreda María Dolores Díaz , Moscarda Eva Josefina Núñez , de Rivas Marta Orejudo , Del Buey Sayas María Ángeles , Puyuelo Francisco Javier Ascaso
Published: January 2022

Purpose

To describe corneal changes after birth trauma from forceps delivery, using anterior segment optical coherence tomography (AS‐OCT), in order to reduce the risk of potential anisometropic amblyopia.

Methods

A 73‐year‐old female patient came to the ocular surface section consulting for dry eye disease symptoms. At the slit lamp examination, a vertical endothelial stria was observed in the right eye. After an exhaustive anamnesis, the patient referred having a traumatic birth in which forceps had been used.

Results

An AS‐OCT was performed, showing a vertical rupture in the Descemet membrane secondary to traumatic birth with forceps.

Conclusions

Descemet’s membrane rupture can cause corneal oedema which usually clears over time, but those ruptures often persist. The residual corneal changes can result in anisometropia and the main cause of vision loss after such injury is anisometropic amblyopia. The AS‐OCT is a useful diagnostic tool to detect these alterations at early stages.

Bibliography

Sarma P, Borgohain M, Tayab S, Sangma CA. Descemet's membrane rupture secondary to forceps‐induced birth injury. Indian J Ophthalmol. 2020;68(10):2253. https://doi.org/10.4103/ijo.IJO_149_20

Alobaidy R, Srinivasan S. Forceps‐induced birth injury to the cornea. BMJ Case Rep. 2014;2014:bcr2013201786. Published 2014 Apr 9. https://doi.org/10.1136/bcr‐2013‐201786
Blinking rate with connected glasses in non‐dry eye and dry eye anomalies in healthy volunteers
Authors: Bremond‐Gignac Dominique , Candice Olsak , Sébastien Darmon , Christophe Caquineau , Philippe Peyrard
Published: January 2022

Purpose

Blinking rate is an essential physiopathological mechanism aiming to maintain a quality tear film layer for ocular surface. The blinking rate may vary with age, environment, medications, ocular surface conditions or anomalies and individuals. Various studies demonstrated how dry eye the most common ocular surface anomaly affects the blinking rate. As we know dry eye is a common pathology in general population, we included healthy volunteers. Our aim is to study blinking rate with connected glasses in healthy volunteers with dry eye and non‐dry eye anomalies.

Methods

In our study, we selected and included 20 healthy volunteers with 40 eyes (of 25) with signed informed consent, from 10 to 40 yo (mean age 25,5 yo) assessing some of the volunteers may present dry eye anomalies. A signed consent was obtained according to legal regulation. A complete ocular examination was performed including automated NIBUT and Meibography with Lacrydiag (Quantel). The volunteers accepted to wear the connected glasses “Prudensee” (Ellcie Healthy) during one hour in practical day life. Then the collected data were analyzed with an algorithm. The connected glasses integrate an infrared oculometer that measures blinking rate. They also integrate a gyroscope and an accelerometer useful for head speed however mt used in the study.

Results

Of the 20 subjects, 9 were diagnosed with mild to moderate dry eye anomalies. The blinking rate was significantly increased of 36% comparing to the 11 subjects with no ocular surface anomalies. Blinking rate measured was increased statistically significative in the 3 groups of age 10–20 yo, 20–30 yo and 30–40 yo and a marked trend in dry eye subjects.

Conclusions

Our study demonstrated an increase in blinking rate in subjects with dry eye anomalies. Further studies with connected glasses are needed to evaluate blinking rate in various anomalies of ocular surface with larger number of subjects.
Anterior segment optical coherence tomography findings after penetrating keratoplasty
Authors: Meriem Ouederni , Ammar Hamdi Ben , Fehmy Nafaa , Maamouri Rym , Hela Sassi , Monia Cheour
Published: January 2022

Purpose

This study aimed to assess the contribution of early anterior segment optical coherence tomography (AS‐OCT) after penetrating keratoplasty (PK) by analyzing the appositions of posterior graft‐host junction (GHJ), the tomographic aspect of the graft and the iridocorneal angle (ICA).

Methods

A prospective cross‐sectional study including 33 eyes of 32 patients treated with penetrating keratoplasty for various preoperative diagnosis (hydrops, keratoconus, bullous keratopathy, infectious keratitis, ocular trauma, corneal perforation, corneal dystrophy and graft failure). All patients underwent complete ophthalmic examination. Early AS‐OCT (Day 1‐10 postoperative) was done to assess the posterior GHJ, the central corneal thickness, the posterior graft corrugations and the ICA. GHJ patterns were classified as well‐apposed, and mal‐apposed (gap, step, and protrusion). Tomographic features were correlated to best‐corrected visual acuity, and postoperative complications.

Results

The mean early postoperative central corneal thickness was 643.63 μm. Posterior corrugations were found in 47% of cases, in patients with graft thickness higher than 590 μm. ICA was open except in 4 eyes, among them, two eyes presented anterior synechia, and developed ocular hypertension and graft rejection. A total of 132 graft‐ host cross‐sections were analyzed. 67% were well‐apposed and 33% were mal‐apposed. Steps have been noted in 8 eyes, followed by Gapes in 3 eyes, and Protrusion in 2 cases. Graft‐steps were present in 4 GHJ and all of these patients had keratoconus as a preoperative diagnosis. Among them, one eye underwent surgical revision for persistent graft edema. Host‐steps were detected in 4 mal‐apposed junctions. Best‐corrected visual acuity showed significant difference with the gap and step patterns of malapposition junctions.

Conclusions

AS‐OCT is a non‐invasive imaging tool offering high‐resolution corneal imaging. It visualizes the posterior GHJ and ICA beyond a non‐transparent cornea. It is useful for evaluating and monitoring the PK outcomes allowing early detection and management of postoperative complications.
Association between physical activity/exercise and dry eye disease: a scoping review
Authors: Navarro‐Lopez Sergio , Moya‐Ramón Manuel , Gallar Juana , Aracil‐Marco Adolfo
Published: January 2022

Purpose

To find evidences of the potential association between physical activity/exercise (PA/E) and dry eye disease (DED).

Methods

A literature search was performed according to PRISMA guidelines on PubMed and Scopus, covering all the papers published up to May 2021. An extensive series of descriptors related to both, PA/E and dry eye were combined. The quality of the reports was analyzed according to the PEDro scale.

Results

A very limited number of publications related to the topic could be found. Most were observational and cross‐sectional studies. In most of them, PA/E was self‐reported using non‐validated instruments or questionnaires asking for PA/E characteristics (frequency, duration, intensity, etc.) below the recommendations on PA/E for health by the World Health Organization. Many studies focused on video‐display terminals or sedentary time, rather than on PA/E itself, and only in one of them the potential association between PA/E and DED was clearly analyzed. A cross‐sectional, interventional study was also found. In some works, the reverse association, that is, the impact of DED‐associated pathologies, such as Sjögren syndrome on PA/E was reported.

Conclusions

Published literature relating PA/E and DED is scarce and its quality is limited to extract clear associations between PA/E and DED. Better study design and instruments are needed for future works. Given the current prevalence of DED and the efforts of health administrations to promote PA/E among the general population, the potential association between these two variables deserves further and deeper analysis.
Plasma rich in growth factors (PRGF ‐ENDORET®) to rescue necrotized orbital dermis‐fat grafts
Authors: Soares Ricardo Machado , Prazeres Sandra
Published: January 2022

Purpose

To report the clinical course of three patients treated with topical plasma rich in growth factors (PRGF) to rescue Dermal‐fat grafts (DFG) with graft ulceration (GU).

Methods

Retrospective, case‐series study of three patients diagnosed with GU in DFG and treated with PRGF. Drops were applied 4 times per day and treatment was maintained until the GU resolved. Data were collected from medical records and anterior segment photos.

Results

All patients showed a favorable response to topical PRGF having accomplished full resolution of the GU within a mean of 30 days of treatment (range: 21–35 days). During the full extent of follow‐up, no side‐effects, signs of rejection or necrosis were reported and every patient was pleased with the final aesthetic result.

Conclusions

Our results suggest that PRGF could be an effective treatment for dermal graft ulceration in patients who underwent DFG surgery/implantation, mainly due to its low morbidity when compared to traditional procedures.
Evaluation of corneal backscatter using Scheimpflug imaging in Fuchs' endothelial corneal dystrophy
Authors: Moscarda Eva Josefina Núñez , Boned‐Murillo Ana , Díaz‐Barreda Mª Dolores , El Bakkali Ismael Bakkali , Rivasés Guillermo Pérez , Cisneros Pablo , deRivas Marta Orejudo , Karlsruher Gisela , Del Buey Sayas María Ángeles
Published: January 2022

Purpose

To compare corneal densitometry obtained using Scheimpflug imaging in the eyes of patients with Fuchs' Endothelial Corneal Dystrophy (FECD) versus the eyes of controls without corneal pathology.

Methods

An observational cross‐sectional case‐control study was carried out on 26 eyes of 14 patients with FECD, and 20 eyes of 11 controls in which corneal pathology had previously been ruled out. All patients underwent a Scheimpflug corneal tomography with Pentacam HR. An analysis of the corneal densitometry results is performed by corneal layers divided into anterior (120 µm), central and posterior (60 µm) and in different areas of concentric circumferences: 0–2 mm; 2–6 mm; 6–10 mm; 10–12 mm.

Results

In the FECD group, the mean backscatter of light was higher than the control group in the circumferences of 0–2 and 2‐6 mm in the anterior, central and posterior layers (p < 0.05). No statistically significant differences were found in the 6–10 and 10–12 mm circumferences. In the posterior layer, the total backscatter average was higher in the FECD group (p < 0.05).

Conclusions

Patients with FECD present higher corneal densitometry values than subjects without corneal pathology in the posterior layer of the cornea and in the central circumferences of the anterior, central and posterior layers.
Development of superimposing electroretinogram for identifying the retinal layer causing a decline in visual sensitivity at arbitrary points on the retina
Authors: Suzuki Naoto
Published: January 2022

Purpose

Although the decline in visual sensitivity of the retina can be measured by microperimetry, it is difficult to identify the retinal layer causing this decline. We investigated cryptogenic diseases, such as macular dystrophy, by developing an electroretinogram (ERG) superimposing seven multifocal hexagonal stimulus arrays on the background of a multifocal array.

Methods

This apparatus is made of illumination and photographic optical systems separated by a mirror with a hole. In addition, it is made of a microperimetry optical system and an ERG optical system separated by a cold mirror. The device consists of an Edmund infrared camera EO‐50231, a lens with a 25‐mm focal length, a halogen lamp, an objective lens with a 50‐mm focal length, 4 double convex lenses with a 100‐mm focal length, 2 aperture stops, a mirror, a 45° cold mirror, an 8‐inch monitor and an artificial eye. We deployed a differential amplifier with gain 10, high‐pass filter with a 21.2‐Hz cut‐off frequency, 60‐Hz notch filter and two non‐inverting amplifiers with gains 1001 and 11. Moreover, we used the National Instruments' I/O device USB‐6212, the Nihon Kohden's plate electrode NE‐113A, the Nihon Kohden's electromagnetic shield sheet Y049 and the LabVIEW 2018 software for data retrieval. The background of the ERG software consists of 11 layers and 330 arrays and uses seven arrays as the examination target. The centre of these seven arrays has the same area, with an array directly placed under it on the background; and the system superimposes these arrays. We developed the ERG software, which was able to display the adjusted background from 18.0 to 30.0 mm and it almost did not have the delay time of a flicker stimulation as the frequency was changed from 10 to 100 Hz. The ERG software was shown on an HP Pavilion 32‐inch HDR display.

Results

At the arbitrary position on the fundus, the superimposing ERG was able to measure all waveforms: a wave, b wave, c wave, and photopic negative response. Cone ERG and bright flash ERG were good.

Conclusions

It is expected that the superimposing ERG function would identify the retinal layer causing visual alterations at specific points throughout the retina. Further work towards pre‐clinical animal testing and clinical evaluation are required.
The electroretinography and optical coherence tomography data matching in patients with advanced stages of glaucoma
Authors: Kotelin Vladislav , Petrov Sergey , Zueva Marina , Zhuravleva Anastasiya , Tsapenko Irina
Published: January 2022

Purpose

To determine the specific changes in the parameters of electroretinography (ERG), reflecting various aspects of retinal ganglion cell (GC) function, and optical coherence tomography (OCT), and their correlations in patients with advanced stages of primary open‐angle glaucoma (POAG).

Methods

The study included 35 people (55 eyes) with stages II and III POAG, divided into two subgroups, and 28 healthy age‐matched individuals (32 eyes). Transient and stationary pattern‐electroretinograms (PERG) and photopic negative response (PhNR) were recorded according to the ISCEV Standards (RETIport/scan, Roland Consult). The thickness of the GC complex (GCC) of the macular region was assessed (Heidelberg Spectralis OCT). The correlation analysis of the GCC indicators and the ERG data was performed. Validation for normal data distribution was performed using the Shapiro‐Wilk test. The Student's t‐test was used to compare normally distributed independent samples. Correlation analysis was performed using Pearson's correlation coefficient.

Results

We found a reduction in the amplitude of N95 and P50 waves of transient PERG, the stationary PERG, PhNR, and PhNR/b index, and an increase in the peak latency of the N95 and P50 in both patient groups (p < 0.05). A statistically significant thinning of all layers of the GCC was noted in all the studied sectors (p < 0.01). The most essential morphological/functional correlations we determined between the amplitude of stationary PERG and the thickness of the GCC (r > 0.8; p < 0.01). The results showed moderate correlation relationships between parameters of the transient PERG and GCC (r > 0.4; p < 0.01) and between the PhNR amplitude and GCC thickness (r > 0.5; p < 0.01).

Conclusions

We documented specific changes in the morphological and functional parameters of the inner retina in patients with advanced stages of POAG. The detected regularities can be used as clinical markers of the disease and monitor the efficiency of a chosen therapeutic strategy.
Treatment outcomes of Mitomycin‐C (MMC) augmented bleb needling in failing trabeculectomy blebs in NHS Tayside
Authors: Lim Qi Xun , Vellisaris Stavros , Garnavou‐Xirou Christina , Cobb Caroline
Published: January 2022

Purpose

Trabeculectomy is the gold standard surgical option in managing glaucoma when intraocular pressure (IOP) is uncontrolled with topical anti‐hypertensive. Bleb failure is not uncommon in trabeculectomy. Bleb needling is a relatively straightforward procedure that can be conducted to re‐establish flow from the trabeculectomy.1,2 We aim to investigate treatment outcomes of MMC augmented needling of failing trabeculectomy blebs in NHS Tayside.

Methods

Retrospective cohort study was performed by reviewing clinical notes of all MMC‐augmented bleb needling procedure after trabeculectomy performed in NHS Tayside from May 2012 to June 2016, patients were identified from surgical records. Data were analysed using IBM® SPSS software and R software (R Foundation for Statistical Computing, Vienna, Austria).

Results

111 patients were identified, 34 excluded as they were lost to follo‐ ups or did not have clinical notes.86 eyes (77 patients) were included in this study. Median number of months between index filtration surgery and the first needling was 23 months. Mean IOP was reduced by 32.6% by the end of Year 1 (23.94 vs 16.14) and 40.4% by the end of Year 3 (23.94 vs 14.28).This was statistically significant at the 0.05 level.28 eyes (32.6%) required further surgical procedures to control IOP (repeat trabeculectomy, glaucoma drainage device, cyclodiode). 9 eyes (10.5%) had complications related to needling with 3 hyphema, 2 post‐operative needling spike,and 1 each had bleb leak, aqueous misdirection, choroidal effusion and hypotony respectively.

Conclusions

Bleb needling is a safe procedure that can be carried out re‐establish flow in failing trabeculectomy to achieve satisfactory control.

Bibliography

1. Lin S, Byles D, Smith M. Long‐term outcome of mitomycin C‐augmented needle revision of trabeculectomy blebs for late trabeculectomy failure. Eye. 2018;32(12):1893‐1899.

2. Panarelli J, Vinod K, Huang G, Sidoti P. Transconjunctival Revision With Mitomycin‐C Following Failed Trabeculectomy. Journal of Glaucoma. 2016;25(7):618‐622.
Neuroprotection in a glaucoma model by Saffron extract oral supplementation
Authors: Fernández‐Albarral José A. , López‐Cuenca Inés , Salobrar‐Garcia Elena , Elvira‐Hurtado Lorena , Lozano María Pilar Rojas , Ramírez Ana I. , Ramirez Jose Manuel , De Hoz Rosa , Corral Juan José Salazar
Published: January 2022

Purpose

To study whether saffron extract supplementation can decrease microglial activation signs and reduce retinal ganglion cells (RGCs) loss in a glaucoma model.

Methods

Albino Swiss mice groups; naïve (NG n = 6), saffron naïve (SNG n = 8), laser 3 days (LG3d n = 8), laser 7 days (LG7d n = 6), saffron laser 3 days (SLG3d n = 8) and saffron laser 7 days (SLG7d n = 6). In laser groups, unilateral ocular hypertension (OHT) was induced by OI laser photocoagulation. OHT and contralateral eyes were analysed. Retinal whole‐mounts were processed: (1) Anti Iba‐1 to quantify: Iba‐1 + cells number (Ibacn) in outer segments (OS), outer plexiform layer (OPL) and inner plexiform layer (IPL); Area of retina occupied by Iba‐1 + cells (Iba‐1 RA) in the nerve fiber layer‐ganglion cell layer (NFL‐GCL); Cell body area of Iba‐1+ cells (CbIbac) in OPL, IPL and NFL‐GCL; and Arbor area of Iba‐1+ cells (AAIbac) in OPL and IPL. (2) Anti‐P2RY12 for resident microglia. 3) Anti‐Brn3a to quantify Brn3a+ RGCs number.

Results

No differences were found between naïve groups. LG3d OHT eyes showed significant: increase of Ibacn, Iba‐1 RA and CbIbac and decrease of AAIbac compared to NG. In SLG3d, OHT and contralateral eyes showed a significant reduction of microglial activation signs compared to LG3d. In NG all Iba‐1 + cells were P2RY12+. Compared to NG, in LG3d OHT eyes, the P2RY12 expression was down‐regulated. In SLG3d OHT eyes, saffron extract led to a smaller decrease. In contralateral eyes of LG3d and SLG3d, P2RY12 expression was similar to NG. In LG7d OHT eyes, a significant reduction in the number of Brn3a+ RGCs compared to NG was observed. Saffron extract counteracted this reduction and a significant different were found in SLG7d OHT eyes respect to LG7d OHT eyes. No differences were found between LG7d and SLG7d contralateral eyes.

Conclusions

Saffron extract decreases the morphological signs of microglial activation, down‐regulation of P2RY12 and counteract the RCGs loss. Thus, they reduce neuroinflammation associated with IOP increase and protect RGCs.
Determination of the tonographic effect in the human eye using a pneumatic pressure modulator
Authors: Link Dietmar , Krauss Benedikt , Stodtmeister Richard , Nagel Edgar , Vilser Walthard , Klee Sascha
Published: January 2022

Purpose

The tonographic effect has been observed in several studies in occulopression, repeated tonometry or ophthalmodynamometry. It describes an intraocular pressure (IOP) decrease caused by an artifical IOP increase. In healthy eyes, an IOP drop of 2–3 mmHg/min was reported. However, there are studies that show a reduced decrease of the IOP drop for instance in glaucoma patients. In this work, we present a proof of principle to determine the tonographic effect in healthy eyes by utilizing a novel pneumatic pressure modulator.

Methods

The study was conducted on 8 healthy subjects (4 m, 4 f, 1 eye each, mean age 27.4 ± 7.1 yr). All subjects passed an ophthalmic examination procedure, including visual acuity determination, tonometry, objective refraction, slit lamp examination. Exclusion criteria were myopia < ‐8 dpt, anamnestic surgeries, corneal scars, eye diseases, ocular hypertension, and ongoing ocular local therapy. No anaesthetics were used. A pressure modulator (IOPstim, Imedos Systems GmbH, Jena, Germany) was used to increase the IOP to initially pathologic IOP values of about 35 mmHg (36.6 ± 2.5 mmHg). The applied pressure was kept constant for 2 minutes. The IOP was measured 4 times (at 0s, 40s, 80s, and 120s) using a rebound tonometer (Icare PRO, Icare Finland Oy, Helsinki, Finland). Linear regression was performed to calculate the average IOP decrease within the 2‐minutes interval.

Results

For all 8 subjects, a typical decrease of the IOP was observed during a 2 min constant pressure stimulation. The mean decrease of the pressure profiles was 2.77 mmHg/min (R2 = 0.94).

Conclusions

We successfully applied a pneumatic pressure modulator to determine the tonographic effect in the human eye. For 2 min we measured the mean decrease of the IOP drop with similar values known by the literature. Application of the pneumatic pressure modulator allows the investigation of pathological reduced IOP drops that differ from normal values as shown in this study.
The relationship between 24‐hour mean, peak, trough and clinic intraocular pressure in glaucoma patients
Authors: Ong Zun Zheng , Sharma Rohit
Published: January 2022

Purpose

For years, ophthalmologists have been relying on clinic intraocular pressure (IOP) to manage glaucoma patients. There are studies which have shown that IOP can vary substantially throughout the day. This prospective observational study is to evaluate the relationship between the 24‐hr mean IOP, peak IOP, trough IOP and clinic IOP and the timing of peak and trough IOP in glaucoma patients.

Methods

23 patients diagnosed with glaucoma were recruited and all of them were fitted with a contact lens sensor for 24 hours. The 24‐hr mean IOP of each patient was recorded. The peak, trough and clinic IOP of each patient were recorded as well. The Pearson correlation coefficient between 24‐hr mean IOP and peak IOP, trough IOP and clinic IOP were calculated and analysed. The circadian IOP pattern of glaucoma patients was constructed and analysed to determine the peak and trough.

Results

The Pearson correlation coefficient of 24‐hr mean IOP and peak IOP among our subjects are r(23) = 0.8419 (p < 0.00001). The correlation coefficient between 24‐hr mean IOP and trough IOP is r(23) = 0.8258 (p < 0.00001). However, the correlation coefficient between 24‐hr mean IOP and clinic IOP is r(23) = 0.3608 (p = 0.091). The overall circadian IOP pattern showed peak IOP at 0730 and 1730 and showed trough IOP at 2130.

Conclusions

The 24‐hr mean IOP showed significantly strong positive correlation with peak and trough IOP among glaucoma patients. However, the 24‐hour mean IOP only showed weak positive correlation with the clinic IOP. We can possibly predict the 24‐hour mean IOP in patients based on single peak or single trough IOP reading but measuring a single IOP in clinic might not tell us the 24‐hour mean IOP of glaucoma patients. The best time to pick up peak or trough IOP to correlate with the 24‐hour mean IOP is at 0730/1730 and 2130 respectively.
Study of office hour and non‐office hour intraocular pressure
Authors: Ong Zun Zheng , Sharma Rohit
Published: January 2022

Purpose

One‐off measurements of IOP in clinic by using standard method such as Goldmann applanation tonometry (GAT) are used by clinicians to monitor the progression of glaucoma. It is long known that IOP have fluctuations throughout the 24‐hour period and some studies have shown that IOP values are higher during late evening which is during non‐office hours. We performed a prospective observational study to evaluate the differences of IOP measurement between office hours and non‐office hours and the circadian IOP changes.

Methods

23 patients with glaucoma were invited and their eyes were examined. They were fitted with a contact lens sensor (CLS) and their IOP data were collected for 24 hours. They were allowed to carry on with their normal activities. The differences of the IOP readings during office and non‐office hours of each patient were compared. The peak and trough IOP were also identified.

Results

14 patients (60.9%) had their office hour IOP significantly higher than non‐office hour IOP. The overall mean difference between office and non‐office hour is ‐31.6 mVeq (95% CI: ‐88.3 to 25.1 mVeq, p = 0.27). There are 12 (52.2%) patients who demonstrated peak IOP value in non‐office hour vs 11 (47.8%) patients in office hours. In contrary, 20 (87.0%) patients have their trough level during non‐office hours (late evening).

Conclusions

There is no significant difference between the mean IOP readings during office and non‐office hours but it varies among individuals. Conventional measurement of IOP in clinic is likely to miss peak IOP values in half of the patients and miss trough IOP values in most patients. We need to monitor 24‐hr circadian IOP patterns with contact lens sensor to provide individualised treatment for glaucoma.
Comparison of Goldmann applanation tonometry and Icare tonometry
Authors: Yu Zhaohua , Edenteg Johan , Raeme Faisal , Söderberg Per
Published: January 2022

Purpose

To compare the variation of intraocular pressure (IOP) measured with Goldmann applanation tonometry (GAT) and Icare tonometry, and further determine if the two methods were calibrated to each other.

Methods

Totally 20 subjects within normal IOP range were evenly divided into two method groups. In one group the IOPs were measured only with GAT and in another group only with Icare. With each method, the IOPs were measured at two occasions and at each occasion 3 measurements were performed.

Results

The estimated variance of IOP among occasions with GAT was 7 times lower than that with Icare. The estimated variance among measurements with GAT was 3 times lower than with Icare. The 95% confidence intervals for mean IOPs were 11.9 ± 1.0 mmHg for GAT and 14.2 ± 1.4 mmHg for Icare.

Conclusions

The lower variations among both measurements and occasions with GAT than with Icare, indicate the reliability is different between the methods. The two methods are not calibrated to each other.
Treatment of open angle glaucoma or ocular hypertension with preservative‐free tafluprost/timolol fixed dose combination in a real‐world clinical practice setting: a cross‐country subanalysis
Authors: Oddone Francesco , Fassari Claudia , Iester Michele , Lopez‐Lopez Fernando , Holló Gabor
Published: January 2022

Purpose

The VISIONARY study assessed, in a real‐world clinical practice setting, the efficacy of preservative‐free tafluprost/timolol fixed‐dose combination (PF tafluprost/timolol FC) in adults with open‐angle glaucoma (OAG) or ocular hypertension (OHT) who did not achieve an adequate response to initial prostaglandin (PGA) or beta‐blocker (BB) monotherapy. This analysis examined the results reported by 7 countries (Italy, Hungary, Spain, Russia, UK, Latvia and Norway) enrolling >10 patients.

Methods

Baseline measurements of IOP were recorded in adults (≥18 years) receiving topical PGA or BB monotherapy for OAG/OHT and treatment was switched to PF tafluprost/timolol FC. IOP was measured at Weeks 4, 12 and 24 during routine ophthalmology visits. The primary endpoint was mean absolute change in IOP from baseline at Month 6, post‐treatment switch. Secondary endpoints included adverse event (AE) reporting and tolerability.

Results

Change in the mean IOP from baseline at Month 6 was 5.7 mmHg (24.9% reduction) for the overall population. Percentage reduction in IOP for the individual countries ranged from 22.3–31.8%. A statistically significant reduction in IOP from baseline was observed at all time points among patients from all countries. The highest percentage reduction in IOP was seen in Latvia at Month 6 (31.8%). Patient‐assessed tolerability was very good/good in 94% of patients. Most reported AEs were mild/moderate in severity and had resolved by the end of the study period.

Conclusions

In a real‐world clinical practice setting, PF tafluprost/timolol FC provided effective and well‐tolerated treatment for OAG/OHT patients insufficiently controlled on BB or PGA monotherapy. Results were consistent across all countries included in the study.

Bibliography

Oddone F, et al. Treatment of Open‐Angle Glaucoma and Ocular Hypertension with Preservative‐Free Tafluprost/Timolol Fixed‐Dose Combination Therapy: The VISIONARY Study. Adv Ther.2020;37(4):1436‐51
Evaluating variance in the medical and surgical management of neovascular glaucoma
Authors: Lee Elsa , Ansari Abdus Samad , Nagi Gurnoor , Ramji Saajan , Jackson Timothy , Kailani Obeda
Published: January 2022

Purpose

There remains a significant paucity in data on the epidemiology and management of neovascular glaucoma (NVG). We aimed to describe NVG incidence rates and establish variance in the medical and surgical management of NVG over a 6‐year period, in the context of pathway modifications implemented in response to the COVID‐19 pandemic.

Methods

Patients diagnosed with and treated for NVG at our centre between January 2015 and April 2021 were identified. Data on patient demographics, co‐morbidities, aetiology and intervention were extracted. Crude incidence rates were calculated. Variation in the form of intervention and severity of disease practice was studied. Multivariate regression modelling was used to look for associations with disease potentially influencing practice.

Results

Five‐hundred seventy seven patients (M:F 327:250) were included with mean age (SD) 70.26 (12.62), baseline cup‐to‐disc ratio (CDR) 0.75 (0.23), and intraocular pressure (IOP) 28.08 mmHg (14.01). Majority of patients were diabetic (63.9% n = 368). Retinal vein occlusion was identified in 35.0% (n = 203). NVG incidence in the 5 years pre‐COVID were 2.5/100 000 (2015), 4.9/100 000 (2016), 7.8/100 000 (2017), 11.5/100 000 (2018) and 15.8/100 000 (2019) (p < 0.0001), and during COVID 11.8/100 000 (2020). Between 2018–2019 and 2020–21, there appeared to be an increasing trend towards implementing anti‐VEGF therapy and alternate forms of glaucoma surgery. Diabetes was associated with higher rates of surgical intervention (OR = 3.69, 95% CI 1.40–9.67, p = 0.008). Conversely, patients aged 50–74 were less likely to undergo surgery (OR = 0.46, 95% CI 0.21–0.99, p = 0.048).

Conclusion

Incidence rates of NVG appear to have increased, with a larger proportion of patients requiring surgical intervention. Discrepancies in these rates suggest a cohort of patients lost during the pandemic; these delayed presentations are likely due to patient reluctance and pandemic workforce redeployment.
Glaucoma clinical research: Trends in treatment strategies and drug discovery
Authors: Freiberg Josefine Clement , Storgaard Line , Tran Thuy Linh , Hauser Alexander S. , Kolko Miriam
Published: January 2022

Purpose

To investigate trends and progresses in glaucoma research.

Methods

All clinical trials with glaucoma covered by Clinicaltrials.gov and Australianclinicaltrials.gov initiated before 1 January 2021 were included. Trials evaluating glaucoma treatment were separated from non‐treatment trials and divided into three major categories: laser‐, surgical‐ and medical treatment. New medical treatment compounds and targets were identified and subcategorized according to treatment strategy; intraocular pressure (IOP)‐lowering, neuroprotective or vascular. The phase transition success rates were calculated.

Results

1537 trials were identified. 63% (n = 971) evaluated glaucoma treatment, of which medical treatment accounted for the largest proportion (53%). Most of the medical trials evaluated IOP‐lowering compounds, while trials evaluating neuroprotective or vascular compounds accounted for only 5% and 3%, respectively. 88 unique new compounds were identified. Phase I, II and III transition success rates were 63%, 26% and 47%, respectively.

Conclusions

Clinical trials in glaucoma have increased significantly over the last 30 years. All three main treatment strategies were represented among the recently evaluated compounds, but clinical trials in neuroprotection and vascular modalities are still sparse. In addition to traditional medicines, dietary supplements and growth factors are also evaluated for a potential anti‐glaucomatous effect. Phase II and III success rates were below previously reported success rate for all diseases and ophthalmology in general. A stricter phenotyping of patients can improve the success rates in glaucoma and ophthalmology research and gain a better understanding of treatment responders and non‐responders.