bluuebunny/crossref_metadata_2025 huggingface dataset:
Matching algorithm utilised in the leros study of idebenone efficacy in leber hereditary optic neuropathy
Authors: Newman Nancy , Llòria Xavier , Silva Magda Joana , Yu‐Wai‐Man Patrick , Carelli Valerio , Klopstock Thomas
Published: January 2025

Aims/Purpose: Randomised, placebo‐controlled trials are the gold standard for evaluating treatment efficacy; however, low patient numbers can limit this approach in rare diseases, such as Leber hereditary optic neuropathy (LHON). To overcome this, in the LEROS study1, outcomes of idebenone treatment in LHON patients were compared to those from an external, untreated, natural history (NH) cohort. Here, we describe the matching algorithm used to ensure comparability between cohorts based on time since the onset of symptoms (OoS), a major factor influencing outcomes in LHON.

Methods: As previously described1, untreated NH eyes from two case record surveys were eligible for matching if they fulfilled LEROS inclusion/exclusion criteria. Separate algorithms were developed for subacute/dynamic and chronic eyes.

Results: A NH visit pair (VP) consisted of a baseline visit (BLV), and a follow‐up visit (FUV) in which the FUV was within ±3 months of a specified analysis timepoint (e.g., 12‐ or 24‐months). As NH eyes were untreated, any assessment after OoS could be used as a BLV if fulfilling the criteria below. The same eye could be eligible for analyses at other timepoints.

For subacute/dynamic analyses, average time from OoS (2nd affected eye) to BLV was calculated in LEROS eyes (onsetL). NH VPs were selected from eyes with a BLV < 1 year from OoS. If an eye had multiple eligible VPs, the one with time from OoS to BLV closest to onsetL was selected.

For chronic analyses, NH VPs were categorised into bins of > 1–2, > 2–3, > 3–4, and > 4–5 years according to time from OoS for each possible BLV. In case several VPs fell into the same bin, the BLV closest to the midpoint of the bin was selected.

Conclusions: These algorithms ensured that time from OoS to BLV was comparable between the LEROS and NH cohorts for each analysis and allowed comparison of idebenone treatment efficacy against an untreated control group.

References

Yu‐Wai‐Man P, et al. Cell Rep Med. 2024;5:101437.
Prevalence of amblyogenic risk factors among children aged 3.5–5.5 years in scotland who fail their vision screening
Authors: Conway Miriam , Pentland Lee , Edgar Dave , Shah Rakhee , Evans Benjamin , Evans Bruce
Published: January 2025

Aims/Purpose: Scotland, with a population of ~5.5 million, has a comprehensive vision screening programme by orthoptists for children aged 3.5‐5.5 years, taken up by ~85% (40,000‐50,000 annually). Tests include presenting vision, cover test, and other orthoptic evaluations. Screening failures are referred for an eye examination, including cycloplegic refraction, by an optometrist or, infrequently, an ophthalmologist. Our aim is to report the prevalence of amblyogenic risk factors (ARF), in children who failed screening and completed an eye examination.

Methods: Based on AAPOS criteria, the following ARF were applied: constant manifest strabismus or any of the following refractive states: hyperopia (spherical equivalent refraction, SER) > 4.00D (in one/both eyes), astigmatism > 1.75DC (in one/both eyes), anisometropia > 1.25DC for astigmatism and > 1.25D (SER) for hyperopic or mixed (one eye hyperopic, the other myopic) anisometropia. 2021/22 school year data, from Scottish Health Boards containing 87% of Scotland's population, are reported.

Results: 36,270 children completed vision screening, 78.9% of all eligible children. 8,130 (22.4%) children failed screening and were referred for eye examination, with data returned and analysed for 5,310 (65.3%). The overall prevalence (95% CI) of children having at least one ARF was 5.06% (4.84‐5.29), and for at least two, three and four ARFs was 1.62% (1.49‐1.76), 0.27% (0.22‐0.33) and 0.04% (0.03‐0.07) respectively. Among children with an ARF, 35.1% had hyperopia > 4.00D, 48.2% had astigmatism > 1.75D, 26.6% had hyperopic anisometropia, 12.6% had astigmatic anisometropia, 2.0% had mixed anisometropia, and 13.7% had constant manifest strabismus.

Conclusions: In this predominantly Caucasian population 5.06% (95% CI: 4.84‐5.29%) of Scottish children (3.5 – 5.5 years) have at least one ARF. The high prevalence of ARFs validates the importance of carrying out a universal vision screening programme.
Choroidal thickness in myopic children: one‐year follow‐up study with 0.01% atropine eye drops
Authors: Simonavičiūtė Dovilė , Gelžinis Arvydas , Grzybowski Andrzej , Žemaitienė Reda
Published: January 2025

Aims/Purpose: Atropine eye drops of various concentrations are widely used to slow the progression of myopia, yet the precise mechanism through which atropine achieves this control remains unclear (1). Studies have shown that choroidal thickness (ChT) decreases as myopia progresses (2) and atropine eye drops have been shown to increase choroidal thickness (3).

Methods: Healthy children aged 6‐12 years with cycloplegic spherical equivalent (SE) from ‐0.5 D to ‐5.0 D and astigmatism ≤1.5D were included. Participants were assigned to the control group or 0.01% atropine eye drops group. The atropine group received 0.01% atropine eye drops once in the evening for 1 year. ChT was assessed in 9 areas using the Early Treatment Diabetic Retinopathy Study (ETDRS) automated grid layout with swept‐source optical coherence tomography (SS‐OCT) at the baseline and after 1‐year follow‐up. Only measurements of the right eye were analyzed.

Results: 31 children were in the control group and 35 in the 0.01% atropine group. The median age was 10 (6‐12) years in the control group and 10 (7‐12) years in the 0.01% atropine group (p = 0.880). There were 22 girls in the control group and 20 in the 0.01% atropine group (p = 0.244). Baseline ChT in all 9 areas were similar between the groups (p > 0.05). After 1‐year follow‐up, changes in choroidal thickness remained similar in all 9 areas between the control and 0.01% atropine groups (p > 0.05).

Conclusions: The administration of 0.01% atropine eye drops did not result in a significant change in ChT over 1‐year follow‐up period compared to the control group in myopic children. Future research should focus on longer follow‐up periods and explore different concentrations of atropine to fully understand its effects on ChT.

References

Upadhyay A, Beuerman RW. Biological Mechanisms of Atropine Control of Myopia. Eye Contact Lens. 2020 May;46(3):129‐135. doi: 10.1097/ICL.0000000000000677. PMID: 31899695; PMCID: PMC7176345.

Gupta P, Saw SM, Cheung CY, et al. Choroidal thickness and high myopia: a case‐control study of young Chinese men in Singapore. Acta Ophthalmol. 2015;93(7):e585‐e592. doi:10.1111/aos.12631

Li W, Jiang R, Zhu Y, Zhou J, Cui C. Effect of 0.01% atropine eye drops on choroidal thickness in myopic children. J Fr Ophtalmol. 2020;43(9):862‐868. doi:10.1016/j.jfo.2020.04.023
Joubert syndrome: A case report
Authors: Sopeña‐Pinilla Maria , Ciubotaru Olga , Bestué Ana Pueyo , Bestué Ignacio Pueyo , Fernandez‐Velasco Diego , Gracia Victor Mallen , Cervilla Jose Javier Bermudez , Merino Andres Biescas , Rius Nuria , Raez Carmen Ila
Published: January 2025

Aims/Purpose: To report the case of a 13‐year‐old girl with Joubert syndrome presenting with a retinal detachment, emphasizing the importance of early recognition and intervention in preventing permanent vision loss.

Methods: This is a retrospective case report.

Results: A 13‐year‐old female with a known diagnosis of Joubert syndrome presented to the emergency department with acute visual disturbances and a significant decrease in visual acuity. Fundoscopic examination revealed a retinal detachment in the left eye, suspected to be of tractional origin or associated with coloboma‐related leakage. Diagnostic imaging included optical coherence tomography (OCT). The patient underwent a 360° scleral buckle, cryoretinopexy, and transscleral drainage of subretinal fluid.

Examination confirmed the presence of a tractional retinal detachment with potential contribution from coloboma‐related leakage. Surgical intervention was successful, resulting in the reattachment of the retina and stabilization of the patient's vision. Post‐operative follow‐up indicated satisfactory recovery and maintenance of retinal attachment.

Conclusions: This case highlights the necessity for healthcare providers to be vigilant for ocular complications in patients with Joubert syndrome. Although retinal detachment is uncommon in these patients, its prompt identification and treatment are critical to preserving vision. The successful outcome underscores the importance of comprehensive ophthalmologic assessment and timely management. Further research into the ocular manifestations of Joubert syndrome and the development of monitoring guidelines is needed to ensure timely intervention and optimal patient outcomes.
Digital devices and the myopia epidemic in children: Short‐ and long‐term effects of use and strategies to manage ocular symptoms
Authors: Monleón Claudia Hernández‐Barahona , Navarro Damián García , Plata Carlos Santana , Rufas Inés Munuera , Pérez Elisa Funes , Merino Jacobo Yañez , Sopeña‐Pinilla Maria , Ciubotaru Olga , Bestué Ana Pueyo , Pueyo‐Bestué Ignacio
Published: January 2025

Purpose: The prevalence of myopia is increasing around the world, stimulating interest in methods to slow its progression. The primary justification for slowing myopia progression is to reduce the risk of vision loss through sight‐threatening ocular pathologic features in later life. By 2050 over 5 billion individuals 50% of the world population will be myopic according to the estimations.

Methods: Literature searches in the PubMed Cochrane Library, and clinical trial databases with no date restrictions, but limited to articles published in English, Spanish and French, were published last on May 1, 2023. The searches yielded 215 citations, 112 of which were reviewed in full text by the first author. Ten articles met the criteria for inclusion (randomized or nonrandomized comparative studies, or case series with a minimum 400 patients; evaluating awareness of increasing myopia prevalence, perceived efficacy and adoption of available strategies).

Results: The 10 included studies consisted of 3 randomized clinical trials, 3 nonrandomized comparative studies, 3 case series, and 1 global survey of clinical management. 6 papers investigated the association between screen use and myopia in the context of other near work activities. The combined effect of near work showed an increased ratio for myopia development. 2 papers focused on evaluate the evidence for association between time outdoors exposure and the reduction risk of onset of myopia. Finally, 2 papers evaluated the awareness of increasing myopia and its consequences showing that each additional 1 D of myopia is associated with a 58%, 20%, 21%, and 30% increase in the risk of myopic maculopathy, open‐angle glaucoma, posterior subcapsular cataract, and retinal detachment, respectively.

Conclusions: From our results, we can conclude that within our samples of children studies, increased screen use is associated with myopia development. The effect of combined near work was decreased by outdoor exposure. The risks of digital devices on myopia and the protection by outdoor exposure should become widely known. Further advocacy and collaboration with policy makers, health regulatory bodies, and industry is needed to enhance accessibility and affordability of treatment options to address the growing health burden of the myopia epidemic.
Spontaneus haematoma in lower rectus muscle
Authors: Ortega Aranzazu Caro , de Lara Sánchez Sofia Sánchez , Prades Gemma Ortega , Casado Francisco Calleja , García Amparo Lanuza
Published: January 2025

Aims/Purpose: Spontaneous orbital haematomas are rare, especially in adults. They cause proptosis and often diplopia and limited motility of the extraocular muscles. Diagnosis is made by radiological tests.

Methods: A 35‐year‐old woman attended the emergency department for proptosis of the left eye (LE), sudden headache and vomiting. She had a history of migraines, without previous trauma or vascular risk factors. Examination revealed an inferior left orbital haematoma, slight exophthalmos, motility deficit in supraversion of the LE and vertical diplopia. The rest of the ophthalmological and analytical examination was unaltered.

The MRI showed a lesion in the left IR, very posterior, localised and with a hyperintense rim that also affected the medial rectus.

Results: It is decided to treat with rest and systemic anti‐inflammatory drugs. After one week, there was still mild diplopia at supraversion, no exophthalmos, no pain on eye movements, and a slight haematoma was seen in the left lower orbit. A new MRI was performed one month after the episode and the lesion had returned.

Conclusions: Orbital haematoma is a rare entity and may be related to the Valsalva manoeuvre. It is important to investigate history of injury, vascular risk factors, the use of antiplatelet drugs; and also to rule out possible underlying vascular malformations or additional injuries by radiological tests.

Idiopathic spontaneous haematoma is diagnosed in the absence of such a history. Haematomas have been described in the extraocular muscles, most of which are located in the IR, as in our patient. Radiological study is decisive for diagnosis and control. These lesions generally regress spontaneously, although there is the possibility of surgical intervention if the pathology persists.

References

Chan, H. H. L., Hardy, T. G., & McNab, A. A. (2019). Spontaneous Orbital Hemorrhage Related to the Extraocular Muscles. Ophthalmic plastic and reconstructive surgery, 35(3), 256–261.
Association of strabismus and congenital cataract in a 2‐year‐old girl
Authors: de la Torre Marta Vela , Shadvar Samira Ketabi , Fernández Jessica Palomares , Muñoz Noelia Montaña , González Olga Martínez , Fiz Jesús Pérez , de Andrade Pérez Marina Pardo , Egusquiza Pablo Ysart , González Miguel Herrero
Published: January 2025

Aims/Purpose: The objective of this study is to evaluate the clinical case of a 2‐year‐old girl referred from pediatrics due to an asymmetric Hirschberg test, analyze the diagnostic findings, and describe the management of her ophthalmological condition.

Methods: A detailed clinical evaluation was conducted, including family history, ophthalmologic exams, imaging studies, and genetic tests. The girl was monitored from 8 months to 24 months of age. Eye movement exams, cover test, autorefractometry under cycloplegia, biomicroscopy, metabolic studies, and genetic testing were performed.

Results: At 8 months, the patient presented with orthotropia and symmetrical Hirschberg, with marked epicanthus and a normal fundus. At 14 months, the cover test revealed 15° exotropia with alternating dominance. Autorefractometry under cycloplegia showed myopia and astigmatism: right eye ‐2.75 ‐1.50 at 80°, left eye ‐2.00 ‐1.50 at 110°, and she was prescribed glasses. At 15 months, biomicroscopy showed punctate opacities in the lens. The metabolic study was normal, but genetic testing identified a probably pathogenic variant in the MAF gene associated with type 21 cataract. Currently, exotropia is controlled with glasses. The best corrected binocular visual acuity is 0.5.

Conclusions: The management of this patient underscores the importance of comprehensive evaluation and multidisciplinary follow‐up in cases of strabismus and congenital cataract with a family history. In this case, rare associations such as congenital cataracts associated with the MAF gene, myopia, and exotropia are found.
Clinical and multimodal imaging findings in tilted disc syndrome
Authors: Aoun Safa Ben , Ferchichi Molka , Maamouri Rym , Fendouli Ines , Selmi Slim , Cheour Monia
Published: January 2025

Aims/Purpose: To describe the clinical and multimodal imaging findings in tilted disc syndrome (TDS).

Methods: A retrospective observational case series including 14 eyes of 7 patients diagnosed with TDS. All patients had complete ophthalmological examination, including fundus photographs, swept‐source optical coherence tomography (SS‐OCT), and automated perimetry. In addition, optical coherence tomography angiography (OCTA) information was acquired for 4 eyes.

Results: The mean age was 48.71 ± 16.10 years. The mean refraction was ‐3.92 ± 2.51 diopters, with 85.7% (7/8) of patients being myopic. Disc pallor and blurring of optic margins were both noted in 57.1% of the cases. Visual field (VF) defects were found in 71.4% of the cases, including blind spot enlargement (42.9%), scotomas (14.3%), and a combination of both (14.3%). On SS‐OCT, peripapillary pigment epithelial detachments were found in 85.7% of the cases. The mean optic nerve head area was 1.78 ± 0.35 mm2. The mean horizontal and vertical cup‐to‐disc ratios were 0.26 ± 0.19 and 0.28 ± 0.26, respectively. The peripapillary retinal nerve fibers layer (pRNFL) was thickened in 5/14 eyes (35.7%) and thinned in 7/14 eyes (50%). All eyes with blurred disc margins had thickened pRNFL, and all eyes with thinned pRNFL had VF defects. Thickening was exclusively located in the nasal and inferior sectors, while thinning was more predominant in the superior and temporal sectors. OCT‐A showed crowded optic nerve heads with a dense, well‐defined microvascular network.

Conclusions: TDS is associated with myopia, disc pallor, blurring of disc margins, and various VF defects. Eyes with TDS have small disc areas and cup‐to‐disc ratios. The pRNFL thickness tends to increase in the inferior and nasal sectors and decrease in the superior and temporal sectors. More studies with larger patient cohorts are needed to provide detailed insights into the structural and vascular anomalies associated with TDS.
Impact of time to idebenone initiation on visual acuity in leber hereditary optic neuropathy: Post hoc analysis of the leros study
Authors: Carelli Valerio , Yu‐Wai‐Man Patrick , Llòria Xavier , Silva Magda Joana , Klopstock Thomas
Published: January 2025

Aims/Purpose: It is not yet established whether time of idebenone treatment initiation from symptom onset (Ti) impacts the clinical outcome of patients with Leber hereditary optic neuropathy (LHON). LEROS, a Phase IV, open‐label, international, natural‐history controlled study (NCT02774005), assessed the long‐term efficacy of idebenone in the treatment of LHON.1 In this post‐hoc analysis of LEROS study data, we report visual acuity (VA) endpoints by Ti.

Methods: VA endpoints at last visit were assessed as previously described, in idebenone‐treated eyes from the LEROS study with an observation time of 12–24 months (m) and a m.11778G > A mitochondrial DNA mutation.1 In this post‐hoc analysis, eyes were stratified by Ti. No statistical comparisons were performed.

Results: Median [range, n] age at baseline was similar regardless of Ti (0–3m: 32.2y [12.6–49.6, 10]; 3–6m: 36.2y [12.6–62.5, 21]; 6–9m: 37.4y [12.6–64.5, 20]; 9–12m: 33.0y [19.5–49.6, 19]; 12–24m: 32.4y [12.1–60.2, 44]; > 24m: 34.7y [12.4–62.4, 61]). VA endpoints at last visit were also similar regardless of Ti; however, minor differences were observed. Eyes that were 3–6m from symptom onset at treatment initiation had the best median [interquartile range (IQR)] VA at last visit (0–3m: 1.27 [0.40–1.68]; 3–6m: 1.22 [0.30–1.80]; 6–9m: 1.40 [1.02–1.56]; 9–12m: 1.52 [0.98–1.60]; 12–24m: 1.39 [0.58–1.74]; > 24m: 1.32 [0.90–1.62]) and the best median [IQR] VA change from last visit to baseline (0–3m: 0.08 [‐0.20–0.62]; 3–6m: ‐0.20 [‐0.46–0.10]; 6–9m: ‐0.11 [‐0.19–0.00]; 9–12m: ‐0.10 [‐0.48– ‐0.04]; 12–24m: ‐0.09 [‐0.47–0.00]; > 24m: ‐0.06 [‐0.18–0.00]).

Conclusions: LEROS study data provides important insights into the impact of time of treatment initiation on VA outcome. However, given the small number of eyes and large variation in the data, caution must be taken in interpreting these results.

References

Yu‐Wai‐Man P et al. Cell Rep Med. 2024;5:101437.
The retinal structure and visual function in asymptomatic individuals carrying leber hereditary optic neuropathy mutation
Authors: Hedström Johan , Engvall Martin , Williams Pete A. , Nilsson Maria , Venkataraman Abinaya Priya
Published: January 2025

Purpose: To evaluate the retinal structure and visual function in asymptomatic subjects with Leber hereditary optic neuropathy (LHON) mutation. We evaluated macular ganglion cell layer and inner plexiform layer (GCL+IPL) and peripapillary retinal nerve fiber layer (RNFL) and assessed high and low contrast visual acuity and visual field sensitivity.

Methods: A total of 28 asymptomatic carriers (37±20 years), 53.5% females, were enrolled. 100% and 13% contrast visual acuity, visual field sensitivity, and Optic coherence tomography (OCT) were performed. Visual field was evaluated with Humphrey Field Analyzer 3 using SITA 24‐2 strategy with white‐on‐white size III stimuli. OCT imaging was performed with a Zeiss Cirrus 5000 HD‐OCT using macular cube 512x128 scan, and optic disc cube 200x200 scan. The thickness and visual function metrics obtained were analyzed to investigate within‐subject differences. For each subject, the eyes were divided into best and worst based on the visual function parameters and as thickest and thinnest based on the structural measurements.

Results: The mean difference between best and worst eye for 100% and 13% visual acuity were 0.03 ± 0.05 (range: 0 to 0.23) and 0.05 ± 0.06 logMAR (range: 0 to 0.18) respectively. For the mean deviation from visual field measurements varied by 1.11 ± 0.85 dB (range: 0.10 to 3.19) between the eyes. The mean difference between thickest and thinnest eye for GCL+IPL and RNFL were 1.48 ± 1.45 μm (range: 0 to 6) and 3.22 ± 2.85 μm (range: 0 to 9) respectively. All the visual function metrics and the structural measurements displayed small but statistically significant inter‐eye differences (p < .005).

Conclusions: In asymptomatic LHON carriers inter‐eye differences were found in structural and functional measurements. OCT imaging and precise visual function test may provide useful information about disease conversion risk in asymptomatic carriers.
From darkness to light: Reversible bitemporal hemianopia
Authors: de Lázaro Alejandra Antón Guzmán , Antón Maria Teresa Cedazo , Martín Sergio Pernas , Outeiriño Patricia Roig , Hernández Eduardo Conesa , Carretero Manuel Moriche
Published: January 2025

Aims/Purpose: The purpose of this case study is to describe the diagnostic process, surgical treatment, and subsequent recovery in a patient who was being monitored for strabismus due to previous thyroid orbitopathy. This case aims to underscore the importance of early diagnosis and timely surgical intervention in the resolution of visual impairments associated with pituitary adenomas.

Methods: A 53‐year‐old female, under follow‐up for strabismus due to previous thyroid orbitopathy, was noted to have limitations in certain eye movements and diplopia during a routine consultation. Suspecting an exacerbation of orbitopathy, a computed tomography (CT) scan was ordered. The CT revealed a sellar and suprasellar mass, an incidentaloma not seen in a CT performed five years earlier. Visual field testing was then conducted, revealing bitemporal hemianopia. Further evaluation with magnetic resonance imaging (MRI) was performed to better characterize the lesion. The patient was subsequently scheduled for transsphenoidal surgery to excise the tumor.

Results: The patient underwent successful transsphenoidal resection of the pituitary adenoma. Postoperative assessments, including regular visual field testing and MRI scans, indicated a gradual but complete restoration of the visual fields over a three‐month period. Follow‐up showed no recurrence of the tumor, and the patient remained free of visual symptoms.

Conclusions: This case illustrates that bitemporal hemianopia caused by pituitary adenomas can be effectively reversed through surgical intervention. Early identification and prompt surgical treatment are essential to prevent permanent visual deficits and ensure full recovery of visual function. This case also highlights the importance of a multidisciplinary approach in the management of complex neuro‐ophthalmological conditions.
Topical insulin as a treatment for refractory persistent epithelial defects
Authors: Arias‐García Elena , López Ester Fernández , Revert María José Roig , Martinez Cristina Peris
Published: January 2025

Aims/Purpose: To present a case series of patients with persistent epithelial defects (PED) of different etiologies treated with topical insulin after failure of conventional treatments and evaluate its efficacy.

Methods: We reviewed the clinical history of 17 patients with PED that were treated with topical insulin since 2020, refractory to conventional treatments.

Results: Of the 17 patients with PED that we reviewed, 16 of them achieved reepithelization with topical insulin after failure of conventional treatment. Reepithelization mean time was 29 days (range 6‐60 days). Recurrence of the epithelial defect was observed in 2 patients. None of the patients that achieved epithelization needed extra treatment after topical insulin in order to solve the PED. No adverse effects were reported with the use of topical insuline and it was well tolerated.

Conclusions: Topical insulin is a very effective treatment for reepithelization of refractory persistent epithelial defects with good tolerance, no adverse effects, and good availability and cost‐effectiveness in comparison to other treatments.

References

Aynsley TR. THE USE OF INSULIN IN THE TREATMENT OF CORNEAL ULCERS. Br J Ophthalmol. 1945 Jul;29(7):361‐3. doi: 10.1136/bjo.29.7.361. PMID: 18170130; PMCID: PMC513802.

Zagon IS et al. Use of topical insulin to normalize corneal epithelial healing in diabetes mellitus. Arch Ophthalmol. 2007 Aug;125(8):1082‐8. doi: 10.1001/archopht.125.8.1082. PMID: 17698755.

Diaz‐Valle D et al. Topical insulin for refractory persistent corneal epithelial defects. Eur J Ophthalmol. 2021 Sep;31(5):2280‐2286. doi: 10.1177/1120672120958307. Epub 2020 Sep 21. PMID: 32951459.

Diaz‐Valle Det al. Comparison of the efficacy of topical insulin with autologous serum eye drops in persistent epithelial defects of the cornea. Acta Ophthalmol. 2022 Jun;100(4):e912‐e919. doi: 10.1111/aos.14997. Epub 2021 Aug 18. PMID: 34407296.

Wang AL et al. Use of Topical Insulin to Treat Refractory Neurotrophic Corneal Ulcers. Cornea. PMID: 28742619; PMCID: PMC5633504.

NaPier E et al. Neurotrophic keratopathy/ current challenges and future prospects. Ann Med.. PMID/ 35243932; PMCID/ PMC8903790.
Comparison of asymmetric offset versus pupil centered ablation in refractive surgery: A randomized, double‐masked clinical trial
Authors: Rafati Shokoofeh , Hashemi Hassan , Pakbin Mojgan , Hashemi Alireza , Aghamirsalim Mohammadreza , Khabazkhoob Mehdi
Published: January 2025

Purpose: To compare the visual and optical outcomes after femtosecond laser in situ keratomileusis (FS‐LASIK) using an aberration neutral profile with asymmetric offset and pupil center treatments.

Methods: In this randomized double‐blind clinical trial study, 48 (24 cases) and 38 eyes (19 cases) underwent hyperopic astigmatism and myopic astigmatism LASIK. One eye of each individual was randomly assigned to asymmetric offset centration and the fellow eye underwent the pupil center method. The clinical outcomes including uncorrected distance visual acuity, corrected distance visual acuity, safety and efficacy indexes, subjective spherical equivalent and corneal high‐order aberrations were measured at baseline and 6 months postoperatively.

Results: In the myopic group, the mean preoperative spherical equivalent and astigmatism were ‐4.12 ± 0.87 (‐2.88 to ‐6.00) diopters and ‐0.88 ± 0.79 (0 to ‐2.75) diopters, respectively. In the hyperopic group, the mean preoperative spherical equivalent and astigmatism were +0.93 ± 0.59 (‐0.25 to +2.25) diopters and ‐0.73 ± 1.00 (0 to ‐4.25) diopters, respectively. At 6 months postoperatively, the safety and efficacy indexes were similar for centration in myopic and hyperopic LASIK groups. In the myopic group, significant changes were found in horizontal trefoil (p = 0.041) and oblique trefoil (p = 0.031) in favor of asymmetric offset centration treatment.

Conclusions: Femtosecond‐LASIK is a safe and efficacious procedure for treatment of myopic and hyperopic astigmatism. Asymmetric offset and pupil center approaches provide similar visual and refractive outcomes. Myopic astigmatism LASIK with asymmetric offset centration leads to slightly better corneal aberration outcomes.
Topographic determinants of anterior chamber angle narrowing in patients with keratoconus
Authors: Nabovati Payam , Soltan‐Dehghan Hamed , Farzaneh Abdollah , Khabazkhoob Mehdi
Published: January 2025

Purpose: To identify topographic determinants of the anterior chamber angle in a sample of patients with keratoconus.

Methods: Two hundred patients who visited a tertiary eye hospital and were diagnosed with keratoconus, were recruited for this study. First, complete ocular examinations were performed for all patients, including measurement of uncorrected distance visual acuity, objective and subjective refraction, and slit‐lamp biomicroscopy. Then, all study participants underwent corneal imaging by the Pentacam rotating Scheimpflug imaging system. The keratoconus was diagnosed based on distorted keratometric mires, scissoring of retinoscopic reflex, abnormal corneal topography (inferior‐superior asymmetry, focal or inferior steepening, or a bow‐tie pattern with skewed radial axes > 21°) consistent with keratoconus as well as the presence of at least one keratoconus biomicroscopic sign.

Results: The mean age of study participants was 32.40± 8.52 years (15‐60 years) and 69.5% of them were male. No statistically significant difference was found in the anterior chamber angle between males and females (p‐value = 0.447). There was a statistically significant inverse correlation between anterior chamber angle and age (r = ‐0.262, p‐value < 0.001). The mean anterior chamber angle was significantly different among different groups of cone morphology; patients with nipple cone had the lowest mean anterior chamber angle (p‐value = 0.001). Moreover, there was a statistically significant difference in the mean anterior chamber angle among different groups of cone location; the lowest mean anterior chamber angle belonged to patients with central cones (p < 0.001). Anterior and posterior Q‐values were significantly directly correlated with anterior chamber angle (anterior Q: r = 0.122, p‐value = 0.014, posterior Q: r = 0.192, p‐value < 0.001).

Conclusions: Keratoconus patients with nipple and central cones and more negative Q‐values were more prone to anterior chamber angle narrowing. It is recommended that the risk of angle closure be taken into account in this group of patients for diagnostic and treatment procedures.
The influence of strain on human keratocyte redox homeostasis and behavior
Authors: Zhang Qian , Backman Ludvig , Danielson Patrik
Published: January 2025

Aims/Purpose: To study the influence of strain on the expression of specific proteins in human keratocytes and its consequential effects on keratocyte intracellular redox homeostasis and behavior.

Methods: Strain was applied to human keratocytes using the Flexcell® Tension Systems. Proteomics and western blot were used to identify proteins regulated in response to strain. Immunofluorescence (IF) staining and live‐cell imaging were employed to monitor reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨM). Expression of oxidative stress‐related protein, and its influence on nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) nuclear translocation and keratocyte proliferation and migration, were assessed by western blot, IF staining and bromodeoxyuridine (BrdU) assay. Mouse injury models and keratocytes from keratoconus patients were used to assess how strain (intraocular pressure, IOP) influences downstream protein in vivo.

Results: The expression of protein Cytochrome P450 1B1 (CYP1B1) and Aldehyde Dehydrogenase 3 Family Member A1 (ALDH3A1) was significantly upregulated in strained keratocytes. Increased CYP1B1 effectively suppressed H2O2‐induced ROS production and mitigated the dissipation of ΔΨM. ALDH3A1 expression was negatively related to ROS accumulation. When the expression of ALDH3A1 was knocked down, NF‐κB nuclear translocation was promoted, ultimately resulting in increased keratocyte proliferation and migration. Mice and keratoconus patients with increased corneal strain also showed elevated ALDH3A1.

Conclusions: Corneal strain significantly upregulates the expression of CYP1B1 and ALDH3A1. Increased CYP1B1 helps maintain keratocyte intracellular redox homeostasis and subsequently regulates keratocyte proliferation and migration via ALDH3A1.
Perfluorohexyloctane eye drops in treating dry eye disease associated with meibomian gland dysfunction: A post‐hoc analysis of responses in subgroups based on symptoms and signs
Authors: Jie Ying
Published: January 2025

Aims/Purpose: In a randomized trial of dry eye disease (DED) associated with meibomian gland dysfunction (MGD), patients received either perfluorohexyloctane eye drops (n = 156) or sodium chloride (NaCl) solution (n = 156) four times daily. The trial showed that perfluorohexyloctane significantly improved DED signs and symptoms with rapid efficacy and satisfactory safety compared to NaCl. This post hoc analysis evaluated efficacy in subgroups based on signs and symptoms, specifically discordant signs and symptoms.

Methods: Patients were grouped according to median changes in total corneal fluorescein staining (tCFS), eye dryness score (EDS), and ocular surface disease index (OSDI) between baseline and day 57 after treatment. Responses at day 57 were defined as: tCFS Response, decrease of ≥ 3 points from baseline; EDS Response, reduction of ≥ 30% from baseline; OSDI Response, reduction of ≥ 30% from baseline.

Results: In the tCFS ≤ 6 & EDS ≥ 60 group, the tCFS & EDS Response was 52.7% (29 patients) with perfluorohexyloctane vs. 28.4% (19) with NaCl (OR 95% CI: 2.82, 1.33–5.96, p = 0.0068). In the tCFS > 6 & EDS ≥ 60 group, the tCFS & EDS Response was 72.1% (31) vs. 36.6% (15) (OR 95% CI: 4.48, 1.78–11.25, p = 0.0014). In the tCFS ≤ 6 & OSDI ≥ 60 group, the tCFS & OSDI Response was 61.4% (27) vs. 28.2% (11) (OR 95% CI: 4.58, 1.79–11.74, p = 0.0015). In the tCFS > 6 & OSDI < 60 group, the tCFS & OSDI Response was 72.2% (26) vs. 42.9% (15) (OR 95% CI: 3.47, 1.29–9.33, p = 0.0138).

Conclusions: The post hoc analysis showed that perfluorohexyloctane eye drops significantly improved DED symptoms and signs in subgroups where symptoms and signs were discordant, such as those with tCFS ≤ 6 & EDS ≥ 60, tCFS ≤ 6 & OSDI ≥ 60, and tCFS > 6 & OSDI < 60, as well as in cases where both symptoms and signs were more severe, such as tCFS > 6 & EDS ≥ 60.
Efficacy and safety of perfluorohexyloctane eye drops in ametropic patients with dry eye disease associated with meibomian gland dysfunction: A subgroup analysis from a phase 3 clinical trial
Authors: Zhao Shaozhen
Published: January 2025

Aims/Purpose: The randomized clinical trial demonstrated the efficacy and safety of perfluorohexyloctane (SHR8058) eye drops for dry eye disease (DED) associated with meibomian gland dysfunction (MGD). This post‐hoc analysis aimed to evaluate the efficacy and safety of perfluorohexyloctane eye drops in ametropic patients with DED associated with MGD.

Methods: This subgroup analysis based on a randomized, double‐masked, saline‐controlled, phase 3 trial included ametropic patients with DED and MGD. In the original study, participants were randomized to receive either perfluorohexyloctane or 0.6% sodium chloride (NaCl) drops four times daily for 57 days. Primary endpoints were changes in total corneal fluorescein staining (tCFS) and eye dryness score at day 57.

Results: A total of 121 ametropic patients were included (57 in the perfluorohexyloctane group, 64 in the NaCl group). At day 57, the perfluorohexyloctane group showed a significant improvement in tCFS score (mean reduction: −5.2) vs. NaCl (mean reduction: −3.3), with an estimated least squares mean (LSmean) difference of −1.9 (95% CI: −2.7 to −1.1). Eye dryness score improved significantly in the perfluorohexyloctane group (mean reduction: −42.4) vs. NaCl (mean reduction: −26.9), with an estimated LSmean difference of −15.5 (95% CI: −22.1 to −8.8). Additionally, perfluorohexyloctane eye drops alleviated symptoms including pain, awareness of DED symptoms, and frequency of dryness compared to the control. Ocular treatment‐emergent adverse events were similar between groups (15.8% in the perfluorohexyloctane group vs. 14.1% in the NaCl group).

Conclusions: Perfluorohexyloctane eye drops significantly improved both objective signs and subjective symptoms of DED in ametropy patients with MGD, demonstrating favorable efficacy and safety.
Perfluorohexyloctane eye drops for dry eye disease associated with meibomian gland dysfunction: A subgroup analysis by menopausal status from a phase 3 trial
Authors: Shi Xiaoru
Published: January 2025

Aims/Purpose: In a randomized, double‐masked, phase 3 trial (NCT05515471), perfluorohexyloctane eye drops effectively improved signs and symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD). This post‐hoc analysis of the phase 3 trial provides efficacy and safety results by menopausal status subgroup.

Methods: As previously detailed, patients with DED associated with MGD were randomly assigned 1: 1 to receive perfluorohexyloctane eye drops or 0.6% sodium chloride [NaCl]). Primary endpoints were changes from baseline in total corneal fluorescein staining (tCFS) and eye dryness scores at day 57. Menopause was defined as at least 12 consecutive months without menstruation. A random effects model adjusted for center and baseline values analyzed the efficacy data.

Results: In total, 94 patients were menopausal (48 on perfluorohexyloctane, 46 on NaCl) and 151 patients were premenopausal (70 on perfluorohexyloctane, 81 on NaCl). At day 57, premenopausal patients treated with perfluorohexyloctane showed greater decreases from baseline in tCFS score and eye dryness score than the NaCl group, with differences between treatment groups of ‐1.35 (95% CI: ‐2.22, ‐0.48) and ‐14.51 (95% CI: ‐20.85, ‐8.17), respectively. In menopausal patients, decreases from baseline in tCFS score and eye dryness score at day 57 were noted in the perfluorohexyloctane group, with no evidence of between‐group differences (tCFS score difference: ‐0.98, 95% CI: ‐1.98, 0.03; eye dryness score difference: ‐7.09, 95% CI: ‐15.12, 0.94). Perfluorohexyloctane led to significantly greater improvements in burning/stinging sensation, awareness of DED symptoms, frequency of dryness, and ocular surface disease index score in both subgroups. Perfluorohexyloctane were well‐tolerated with similar safety profiles across subgroups.

Conclusions: Perfluorohexyloctane eye drops showed efficacy and well tolerability for DED associated with MGD in both menopausal and premenopausal patients.
Modified descemet's stripping automated endothelial keratoplasty (DSAEK) after failed visco‐assisted dalk: Case report
Authors: Mancini Alessandra , Lucisano Andrea , Giannaccare Giuseppe , Pietropaolo Rocco , Taloni Andrea , Carnevali Adriano , Scorcia Vincenzo
Published: January 2025

Aims/Purpose: This case report aims to describe the posterior lamellar approach to manage stromal interface irregularity after deep anterior lamellar keratoplasty (DALK).

Methods: A 42‐year‐old woman previously underwent DALK with visco‐bubble failed for keratoconus associated with intraoperative perforation. One year after surgery, she presented to our center with loss visual acuity. The recipient bed appeared wrinkled and opaque. The anterior optical surface was regular, with low and regular astigmatism. Endothelial cell density (ECD) could not be assessed. The planned surgical procedure consisted of a modified small diameter (7mm) DSAEK technique, in which only the small optic zone was replaced, resulting in a two‐piece mushroom graft configuration.

Results: Corneal clarity was restored and complete attachment of the donor lamella was achieved. Postoperative best‐ corrected visual acuity (BCVA) reached 20/20. No intraoperative or postoperative complications were reported.

Conclusions: To achieve the clearance of the recipient bed in eyes that have undergone manual DALK, the least invasive surgical strategy should be planned, preserving the healthy corneal tissue of the patient. Small diameter posterior lamellar keratoplasty has a lower incidence of postoperative complications, decreases immunological risk and accelerates functional recovery
Tears as a repository for particulate matter PM 1.0, 2.5 and 10 in an urban environment
Authors: Porru Emanuele , Astolfi Gloria , Ciavarella Carmen , Violante Francesco , Versura Piera
Published: January 2025

Aims/Purpose: This study investigates the potential of tear fluid analysis as a non‐invasive method to monitor air pollution impact on an exposed body tissue, represented by the ocular surface [1,2]. In particular, we characterized the particulate matter (PM) in tears in healthy volunteers exposed or not to an urban environment.

Methods: Twenty healthy volunteers were enrolled from personnel staff, ten were exposed to urban traffic in Bologna, Italy in the period January‐April 2024 for a minimum of 2 hours, and ten were not. A minimum of 5 μL tear were sampled from the lower conjunctival sac, deposited onto glass slides or polycarbonate filters, allowed to dry and stored at room temperature in a sterile Petri dishes, until observation. Scanning electron microscopy (SEM, Zeiss) was employed to analyze and characterize the PM present in the samples. Particles were categorized by size, morphology, and elemental composition using energy‐dispersive X‐ray spectroscopy (EDS). PM analysis and characterization in tears was compared to filters obtained for gravimetric analysis of airborne PM collected via filtration in Milan.

Results: SEM analysis revealed predominantly fine particles (PM2.5), with occasional larger ones (PM10). Elemental analysis identified common PM pollutants such as carbon, oxygen, sulfur, nitrogen, and trace metals like iron and calcium. The particle count per unit area (15 eV, 400x) showed a range of densities across different samples, with a difference in PM levels between exposed and non exposed subjects.

Conclusions: The study demonstrated that SEM analysis of tear samples is a viable method for detecting PM levels in tears, and a notable difference between exposed and non exposed subjects. This highlights the potential role of tear analysis in monitoring environmental pollution. This non‐invasive approach could be pivotal in understanding the impact of air pollution on the ocular surface.

References

M.A. Gutiérrez, D Giuliani, A.A. Porta, D. Andrinolo D, J Ophthalmic Vis Res 2019, 14(4), 419‐427.

O. Girshevitz, N. Cohen‐Sinai, A. Zahavi, Y. Vardizer, D. Fixler, N. Goldenberg‐Cohen, J. Pers. Med. 2022, 12, 1633.
Ultrastructure alteration of post intacs cornea
Authors: Akhtar Saeed , Kirat Omar , Alkanaan Aljohara , Almubrad Turki
Published: January 2025

Aims/Purpose: To Investigate the organization and distribution of lamellae, and collagen fibrils of 3 post‐INTACS‐corneas. INTACS SK were surgically inserted into the cornea to remodel the keratoconus shape of the corneal curvature of three patients.

Methods: Three patients had INTACS inserted with IntraLase femtosecond laser [Advanced Medical Optics (AMO), Santa Ana, CA]. Patient 1 returned to the clinic after 6 years, Patient 2 after 8 and Patient 3 after 9 years due to dissatisfaction with their vision. Each patient was referred for lamellar keratoplasty. The lamellae above the INTACS were removed and were processed for light and electron microscopy. Digital images of lamellae, collagen fibrils and proteoglycans were captured by a bottom mounted camera and analyzed by iTEM software.

Results: The ultrastructure of the epithelium and stroma were similar in both central and peripheral parts of the cornea in all three patients. The epithelium contained a large number of electron lucent spaces in the cytoplasm of the wing cells and basal epithelial cells. A large number of aggregates of fibrillar material were present in the Bowman's layer and throughout the stroma. The lamellae at the anterior stroma were not interconnected and the lamellae in the middle stroma were undulated (or cone shaped) not parallel. In the stroma just above the INTACS insertion, lamellae were completely disorganized and running randomly in the large electron lucent spaces. The CF in this region were small in size and had very large spacing among them.

Conclusions: The epithelium, lamellae and CFs were degenerated in the post INTACS inserted cornea. We believe that insertion of the INTACS disturbed the lamellar organization and uniform distribution of the CFs. This non‐uniform distribution of the CFs increased over time resulting in the impairment of vision. Further research is required to study the gradual changes in the corneal architecture after the insertion of INTACS.
Ultrastructure of long fibers of the peripheral posterior cornea and immunogold localization of BIG‐H3 and alpha‐elastin proteins
Authors: Akhtar Saeed , Kirat Omar , Alkanaan Aljohara , Almubrad Turki
Published: January 2025

Aims/Purpose: This study was conducted to investigate the ultrastructure of the long fibres present at the posterior peripheral cornea and expression of the proteins associated with these fibres.

Methods: Five anonymous‐donor human corneoscleral rims (leftover after corneal transplants) were used in the study. Five pieces (1.5‐mm) from each ring were cut and were fixed in 4% paraformaldehyde + 0.5% glutaraldehyde in 0.1‐M phosphate buffer for transmission electron microscopy (TEM). The tissues were embedded in LR White resin and polymerized under UV light at 4°C for 48 hrs to investigate the ultrastructure and for immunogold localization of BIG‐H3 and α‐elastin proteins with immunogold technique. Semi‐thin and ultrathin sections were cut using RMC PowerTome ultra cut microtome and observed under Olympus BX53 and JOEL JEM‐1400 (HC) respectively. The long fibres were observed in the posterior peripheral cornea at a radial distance of approximately 900μ from the endpoint of Descemet's membrane (DM). Images were captured using a Quemesa 14 Mega and Xarosa 20 Mega Pixel Bottom Mount CCD Camera.

Results: A large number of long fibres with electron dense bands and sheath material were observed above the DM. These fibres contained electron dense fibrillar material and some of the fibers contained collagen fibrils with a banding pattern. The long fibres were strongly labelled with BIG‐H3 antibody but not with α‐elastin antibody. The BIG‐H3 antibody also labelled the microfilaments in the sclera. The α‐elastin antibody strongly stained the central elastic core of the elastic fibres in the sclera.

Conclusions: The long fibres enclosed the collagen fibrils and were strongly labelled with BIG‐H3 protein. The fibres were not labelled with elastin antibody whereas elastic fibres in the sclera were strongly labelled. The presence of the collagen fibrils within the long fibres suggests that the long fibres may be formed by the aggregation of the collagen fibrils and BIG‐H3 protein. These long fibres were not elastic fibers.