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Aims To evaluate the impact of herpes simplex virus (HSV)-induced scar location on bilateral corneal nerve alterations using laser in vivo confocal microscopy (IVCM). Methods Central and peripheral corneal subbasal nerve density (CSND) were assessed bilaterally in 39 patients with unilateral HSV-induced corneal scars (21 central scars (CS), 18 peripheral scars (PS)) using IVCM. Results were compared between patients and 24 age-matched controls. CSND was correlated to corneal sensation for all locations. Results Overall patients revealed significant decrease of CSND in the central and peripheral cornea (9.13±0.98 and 6.26±0.53 mm/mm², p<0.001), compared with controls (22.60±0.77 and 9.88±0.49 mm/mm²). CS group showed a decrease in central (8.09±1.30 mm/ mm²) and total peripheral nerves (5.15±0.62 mm/mm²) of the affected eyes, whereas PS group demonstrated a decrease in central (10.34±1.48 mm/mm²) and localised peripheral nerves only in the scar area (4.22±0.77 mm/mm²) (all p<0.001). In contralateral eyes, CSND decreased in the central cornea of the CS group (16.88±1.27, p=0.004), and in the peripheral area, mirroring the scar area in the affected eyes of the PS group (7.20±0.87, p=0.032). Corneal sensation significantly decreased in the whole cornea of the affected, but not in contralateral eyes (p<0.001). A positive correlation between CSND and corneal sensation was found in all locations (p<0.001). Conclusions Patients with HSV scar demonstrate bilateral CSND decrease as shown by IVCM. CSND and corneal sensation decrease in both central and peripheral cornea in affected eyes, although only in the scar area in PS group. Interestingly, diminishment of CSND was found locally in the contralateral eyes, corresponding and mirroring the scar location in the affected eyes. [ABSTRACT FROM AUTHOR]

AIMS: To comprehensively study the gross anatomy of human corneal innervation. METHODS: Twenty-one specimens, including 12 normal human corneas from seven deceased patients, two eye-bank corneo-scleral buttons, two eye-bank corneo-scleral rims and five post-surgical specimens from three patients with keratoconus were studied. Corneal whole mounts were stained for cholinesterase enzyme using the Karnovsky & Roots direct colouring thiocholine modification of acetylcholinesterase (AchE) technique. RESULTS: Approximately 44 thick nerve bundles were found to enter the human cornea in a relatively equal distribution round the limbus and move randomly towards the central cornea. At the mid-peripheral zone, anterior stromal nerves showed a characteristic budding and branching pattern. After passing through Bowman's zone they were noted to terminate into bulb-like thickenings from which multiple sub-basal nerves arose. The perforation sites were predominantly located in the mid-peripheral cornea. The orientation of sub-basal nerves was mainly vertical at their origin from the perforation sites. Nerves from all directions converged towards the infero-central cornea to form a characteristic clockwise whorl pattern. CONCLUSIONS: This study provides a comprehensive account of the architecture and distribution of nerves in the human cornea. It reconciles some of the existing information obtained from other modalities of investigation and identifies some novel features that provide a more complete picture of corneal innervation. [ABSTRACT FROM AUTHOR]

Purpose: Previously we could show increased numbers and densities of dendritic-like cells (DLCs) in the subbasal nerve plexus of the central cornea in patients with herpetic anterior uveitis (HAU). Now we aimed to explore these and other inflammatory cells seen in this layer in different subtypes of anterior uveitis using in vivo confocal microscopy. Methods: Consecutive eyes of patients with different types of anterior uveitis, HAU, Fuchs' uveitis syndrome (FUS), juvenile idiopathic arthritis (JIA) and human leucocyte antigen (HLA)-B27-related anterior uveitis were examined in vivo with the combination of Heidelberg Retina Tomograph II/III and Rostock Cornea Module. The contralateral eye was used as control. Inflammatory cells were defined on the basis of their morphology: type 1 (DLCs) and type 2 (cell bodies lacking dendrites). Frequencies were evaluated statistically in each group. Results: The difference between means of type 1 cells density of affected eyes in all four groups was significant (one-way analysis of variance (ANOVA) p=0.039). The difference between means of type 1 cell densities of affected eyes in patients with HAU (96.8 ±44.2 cells/mm², n=10) and that of patients with FUS (46.4±38.7 cells/mm², n=17) was significant (Tukey's post hoc p=0.025), whereas the difference between patients with HAU and JIA (53.3±34.5 cells/mm², n=7) and patients with HAU and HLA-B27 (63.1±59.2 cells/ mm², n=10) was not significant (Tukey's post hoc p=0.181 and 0.300). In contrast, the following means resulted from the evaluation of type 2 cells: the difference between means of affected eyes in all four groups was not significant (one-way ANOVA p=0.185). Density means difference of patients with HAU (44.9 ±22.6 cells/mm², n=5) and that of FUS (20.0 ±11.0 cells/mm², n=2) and that of patients with JIA (56.0±18.3 cells/mm², n=2) and that of HLA-B27 (36.1±24.1 cells/mm², n=5) was not significant (Tukey's post hoc p=0.302, 0.877 and 0.739). The contralateral eye of all patient groups showed also an inflammatory cell infiltrate of lesser extent. Conclusions: The high density and morphology of DLCs in the central cornea of patients with HAU assessed by confocal microscopy supports the clinical diagnosis of HAU especially when compared with patients with FUS but not when compared with patients with JIA or HLA-B27. Clinical relevance: This study suggests that the non-invasive confocal microscopy of the cornea is capable of supporting a clinical diagnosis in patients with uveitis. [ABSTRACT FROM AUTHOR]

An 80-year-old Chinese man with high myopia and a history of right eye cataract extraction and superior peripheral iridectomy developed peripheral corneal oedema after a period of aphakia. The peripheral corneal oedema was static over years and did not progress to involve central cornea hence his visual acuity remained stable. The condition was compatible with the relatively rare Brown-McLean syndrome. Specular microscopy showed normal endothelial cell density in the oedematous peripheral as well as central cornea. While anterior segment optical coherence tomography demonstrated the cross-sectional architecture of cornea, Scheimpflug imaging was used to measure the peripheral corneal thickening and to demonstrate increased corneal density as compared with the contralateral normal eye. These investigations not only help better characterise the rare disease, but also in precisely monitoring any disease progression by periodic measurements. [ABSTRACT FROM AUTHOR]

BACKGROUND: The purpose of this study was to use laser scanning in vivo confocal microscopy to elucidate the location and morphology of stromal nerves in the normal human central cornea. METHODS: Analysis was performed via an established database of laser-scanning in vivo confocal microscopy on images of the central cornea of normal subjects. The depth and morphology of the stromal nerves were determined. RESULTS: The population of this study consisted of 99 eyes of 99 healthy subjects (38 male, 61 female). The mean age of the group was 34.7 (SD 13.3, range 13–84) years. Two morphologically different populations of stromal nerves were observed: (1) straight, dichotomous branching nerves; and (2) tortuous nerves with a beaded appearance. The mean recorded depth of straight stromal nerves (186 (SD 66) µm) was significantly deeper than the mean depth of the tortuous stromal nerves (140 (SD 87) µm) (p<0.001). CONCLUSIONS: The current study identified two morphologically distinct stromal nerve populations in the normal human cornea. We hypothesise that the two morphological nerve populations described here may represent functionally heterogeneous nerves. Further research is required to determine if these in fact represent different types of sensory nerves. [ABSTRACT FROM AUTHOR]

We present two patients with a new finding of symmetrical corneal thinning early in the clinical course of iridocorneal endothelial syndrome. Patient 1 was evaluated for uncontrolled angle closure glaucoma of the left eye (OS) status post laser peripheral iridotomy (LPI). After placement of an Ahmed glaucomatous valve and trabeculectomy with mitomycin C were performed, the patient was diagnosed with Chandler syndrome. The patient’s pachymetry at the time of diagnosis revealed stable central corneal thickness (CCT) of 481 μm of the right eye (OD) (baseline 494 μm) and central cornea thinning with CCT of 407 μm OS (baseline 486 μm). Patient 2 was evaluated for ocular hypertension and Chandler syndrome OS was diagnosed. The patient had a good short-term response to LPI and ocular hypotensive medications. This patient was also found to have thinning of his affected cornea with CCT 523 μm OD and 476 μm OS. [ABSTRACT FROM AUTHOR]

Aim To investigate changes in corneal endothelial cell density (CECD) after trabeculectomy. Methods This prospective, observational study followed 117 eyes of 117 patients for 2 years after trabeculectomy. The central cornea was examined by corneal specular microscopy prior to and at every 6 months after the surgery. Survival analysis of patients who exhibited a 10% or less reduction of the postoperative CECD compared with preoperative levels was assessed using the Kaplan-Meier survival curve. A Cox proportional hazards model was used to evaluate prognostic factors for decreasing CECD. Results At baseline, the mean CECD was 2420±357 cells/mm2, while at 6, 12, 18 and 24 months after surgery, the mean CECD was 2324±373 cells/mm2 (p<0.001), 2276±400 cells/mm2 (p<0.001), 2290±398 cells/mm2 (p<0.001) and 2267±446 cells/mm2 (p<0.001), respectively. At 6, 12, 18 and 24 months after surgery, the results of the Kaplan-Meier survival analysis of the 10% loss of CECD from baseline were 91%, 85%, 83% and 77%, respectively. Uveitic glaucoma was a significant prognostic factor for decreasing CECD (p=0.041). Conclusions CECD significantly and continuously decreased after trabeculectomy. [ABSTRACT FROM AUTHOR]

Aims To evaluate the bilateral changes in the sub-basal nerve plexus of the cornea and ocular surface function after unilateral small incision lenticule extraction (SMILE) and transepithelial photorefractive keratectomy (tPRK) procedures. Methods 34 patients were enrolled in the study and underwent unilateral SMILE (21 of 34 patients) or unilateral tPRK (13 of 34 patients). Complete ophthalmic examinations, tear film function tests and Cochet-Bonnet esthesiometry were conducted to assess the effects of the surgeries on the corneal nerves and tear function. Morphological changes were assessed using in vivo confocal microscopy to evaluate the corneal sub-basal nerve plexus and dendritic cells. ELISA was used to measure the tear neuromediators. Clinical and morphological data at each follow-up point were compared with preoperative baseline values. Results All patients who underwent unilateral SMILE or tPRK procedures exhibited bilateral corneal nerve degenerative changes, decreased corneal sensitivity, worsening of dry eye symptoms and changes in bilateral tear neuromediators. In the SMILE group, bilateral corneal sensitivity was positively correlated with corneal nerve fibre length and negatively correlated with dendritic cell area. The dry eye severity was negatively correlated with corneal sensitivity. Tear levels of substance P and nerve growth factor were positively correlated with mean dendritic cell area and dry eye severity, but negatively correlated with corneal sensitivity. In the tPRK group, bilateral corneal sensitivity was positively correlated with corneal nerve fibre density. Conclusions Unilateral refractive surgery may bilaterally affect the morphology and function of corneal nerves and ocular surface status postoperatively. [ABSTRACT FROM AUTHOR]

Background Glaucoma prevalence and subtype profile vary across different racial and ethnic groups. This study provides a comparative evaluation of differences in aqueous humour dynamics (AHD) and ocular biometrics in healthy Chinese and Caucasian adults of two different age groups. Methods Data from two independent studies with identical designs were compared. Cohorts included young adults (20-30 years old, 32 Chinese and 39 Caucasians) and older adults (>50 years old, 37 Chinese and 46 Caucasians). Parameters of AHD and ocular biometrics were evaluated. Group comparisons were made by generalised estimating equation methods. results Differences in young adult Caucasians compared with similarly aged Chinese were thinner central cornea (-29.27 µm, p<0.001), lower intraocular pressure (IOP) (-2.33 mm Hg, p<0.001), larger anterior chamber volume (ACV) (28.78 µL, p<0.001) and faster uveoscleral outflow rate (Fu) (0.82 µL/min, p<0.001). Differences in older adult Caucasians compared with similarly aged Chinese were slower aqueous flow rate (Fa) (-0.28 µL/min, p=0.042), lower IOP (-1.97 mm Hg, p<0.001) and larger ACV (33.15 µL, p<0.001). Considering all subjects together by race, Caucasian subjects had slower Fa (-0.22 µL/min, p=0.035), thinner corneas (-0.52 µm, p=0.003), lower IOP (-2.11 mm Hg, p<0.001), higher ACV (30.39 µL, p<0.001) and faster Fu (0.63 µL/min, p<0.001). Conclusion Differences in AHD and biometrics between Caucasian and Chinese adults include larger ACVs which may contribute to the wider angles reported in Caucasians, and slower Fa rates coupled with faster Fu rates which may contribute to their lower IOP and lower overall risk of glaucoma. [ABSTRACT FROM AUTHOR]

Background/aims: To compare the performance of generative versus retrieval-based chatbots in answering patient inquiries regarding age-related macular degeneration (AMD) and diabetic retinopathy (DR). Methods: We evaluated four chatbots: generative models (ChatGPT-4, ChatGPT-3.5 and Google Bard) and a retrieval-based model (OcularBERT) in a cross-sectional study. Their response accuracy to 45 questions (15 AMD, 15 DR and 15 others) was evaluated and compared. Three masked retinal specialists graded the responses using a three-point Likert scale: either 2 (good, error-free), 1 (borderline) or 0 (poor with significant inaccuracies). The scores were aggregated, ranging from 0 to 6. Based on majority consensus among the graders, the responses were also classified as 'Good', 'Borderline' or 'Poor' quality. Results: Overall, ChatGPT-4 and ChatGPT-3.5 outperformed the other chatbots, both achieving median scores (IQR) of 6 (1), compared with 4.5 (2) in Google Bard, and 2 (1) in OcularBERT (all p =8.4×10-3). Based on the consensus approach, 83.3% of ChatGPT-4's responses and 86.7% of ChatGPT-3.5's were rated as 'Good', surpassing Google Bard (50%) and OcularBERT (10%) (all p =1.4×10-2). ChatGPT-4 and ChatGPT-3.5 had no 'Poor' rated responses. Google Bard produced 6.7% Poor responses, and OcularBERT produced 20%. Across question types, ChatGPT-4 outperformed Google Bard only for AMD, and ChatGPT-3.5 outperformed Google Bard for DR and others. Conclusion: ChatGPT-4 and ChatGPT-3.5 demonstrated superior performance, followed by Google Bard and OcularBERT. Generative chatbots are potentially capable of answering domain-specific questions outside their original training. Further validation studies are still required prior to real-world implementation. [ABSTRACT FROM AUTHOR]

Aim To investigate the interest of chromatic confocal microscopy (CCM) to characterise guttae in Fuchs endothelial corneal dystrophy (FECD). Methods Descemet's membranes (DM) were obtained during endothelial keratoplasty in patients with FECD and pseudophakic bullous keratopathy (PBK). They were compared with healthy samples obtained from body donation to science. Samples were fixed in 0.5% paraformaldehyde and flat mounted. Surface roughness of DMs was quantified using CCM and the AltiMap software that provided the maximum peak (Sp) and valley (Sv) heights, the mean square roughness (Rq) and the asymmetry coefficient (Ssk). Results The physiological roughness of healthy samples was characterised by an Rq of 0.12±0.05 µm, which was two times rougher than in PBK (Rq=0.06±0.03 µm), but both were still flat with a symmetrical distribution between peaks and valleys (Ssk close to 0, npeaks=nvalleys), smaller than 1 µm. In FECD, the maximum peak height was 5.10±2.40 µm, up to 5.8 and 8.3 times higher than the control and PBK, respectively. The maximum valley depth was half than the peak (2.28±0.89 µm). The surface with guttae was very rough (Rq=0.45±0.14 µm) and the Ssk=1.84± 0.43 µm, greater than 0, confirms an asymmetric surface with high peaks and low valleys (npeaks>nvalleys). Moreover, the CCM provided quantitative parameters allowing to distinguish different types of guttae from different patients. Conclusions CCM is an innovative approach to describe and quantify different morphologies of guttae. It could be useful to analyse the different stages of FECD and define subgroups of patients. [ABSTRACT FROM AUTHOR]

We present a case of a male patient in his mid-50s who presented with bullous keratopathy secondary to an anterior chamber intraocular lens, complicated by superimposed honeycomb keratopathy while on ripasudil 0.4%. The bullous keratopathy was characterised by generalised microcystic epithelial oedema, alongside more centrally located, variable-sized macrocystic epithelial oedema with a honeycomb appearance. Discontinuation of ripasudil resulted in the resolution of the honeycomb keratopathy, although with the persistence of pre-existing microcystic corneal oedema. This case highlights the complexity of ripasudil’s effects on corneal endothelium, showing a paradoxical response. Timely identification of ripasudil-induced keratopathy is crucial, particularly in cases when it is started elsewhere, emphasising the necessity for vigilant monitoring and management strategies. [ABSTRACT FROM AUTHOR]

The histopathological findings in five post-mortem eyes with anterior chamber and iris fixation intraocular lenses (IOLS) are discussed. The interval between lens insertion and death ranged from 3 1/2 to 52 months. Clinically the lenses were well tolerated and the surgery was considered to be successful. In one case a vitrectomy was required. Prominent histopathological features included reduced corneal endothelium (five cases), central cornea guttata (one case), dislocation of an anterior chamber IOL (one case), abnormalities of the filtration angle (five cases), non-granulomatous iritis (two cases), and iris atrophy and erosion (five cases). [ABSTRACT FROM PUBLISHER]

We report a case of a woman in her 30s who underwent femtosecond LASIK (laser-assisted in situ keratomileusis) in both eyes to correct her simple myopic astigmatism. After the surgery, both eyes developed diffuse lamellar keratitis, and intensive topical steroids were initiated to control the same. Subsequently, central toxic keratopathy (CTK) developed bilaterally. Three weeks after the surgery, the right eye showed signs of progressive epithelial ingrowth involving the pupillary area. Surgical intervention in the form of flap relift followed by debridement of the epithelial cells and an alcohol interface wash were performed to treat the same. This is the first report of an epithelial ingrowth following CTK after femtosecond LASIK. [ABSTRACT FROM AUTHOR]

We present two cases which underwent complex ocular surface reconstruction to achieve a stable ocular surface. Conjunctival autograft (CAG) procedure was required more than once, in addition to simple limbal epithelial transplantation to address extensive symblepharon in the eyes with total unilateral limbal stem cell deficiency secondary to acid ocular burns. These cases demonstrate that multiple CAGs may be harvested from the contralateral unaffected eye to correct recurrent symblepharon without any donor site complications if the correct surgical technique is adopted. [ABSTRACT FROM AUTHOR]

Objective To establish an automated corneal nerve analysis system for corneal in vivo confocal microscopy (IVCM) images from both the whorl-like corneal nerves in the inferior whorl (IW) region and the straight ones in the central cornea and to characterise the geometric features of cornea nerves in dry eye disease (DED).Methods and analysis An encoder–decoder-based semi-supervised method was proposed for corneal nerve segmentation. This model’s performance was compared with the ground truth provided by experienced clinicians, using Dice similarity coefficient (DSC), mean intersection over union (mIoU), accuracy (Acc), sensitivity (Sen) and specificity (Spe). The corneal nerve total length (CNFL), tortuosity (CNTor), fractal dimension (CNDf) and number of branching points (CNBP) were used for further analysis in an independent DED dataset including 50 patients with DED and 30 healthy controls.Results The model achieved 95.72% Acc, 97.88% Spe, 80.61% Sen, 75.26% DSC, 77.57% mIoU and an area under the curve value of 0.98. For clinical evaluation, the CNFL, CNBP and CNDf for whorl-like and straight nerves showed a significant decrease in DED patients compared with healthy controls (p0.05).Conclusion The proposed method segments both whorl-like and straight corneal nerves in IVCM images with high accuracy and offered parameters to objectively quantify DED-induced corneal nerve injury. The IW is an effective region to detect alterations of multiple geometric indices in DED patients.

A 60-year-old female patient with phacomorphic glaucoma underwent initial medical management to control the intraocular pressure (IOP). After 48 hours, a stable IOP was achieved and subsequently the patient was planned for phacoemulsification followed by intraocular lens implantation. There was initial difficulty while reconstructing the corneal wounds; however, phacoemulsification and IOL implantation were uneventful but during viscoelastic removal, an inadvertent Descemet's membrane detachment involving the central cornea was noted. Postoperatively corneal oedema persisted till 1 week, following which there was a gradual improvement with topical antibiotics, steroids and hyperosmotic agents. At the end of 6 months, the best corrected visual acuity was 20/25 with a central corneal thickness of 580 μm without any need for additional endothelial replacement surgery. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) can cause recalcitrant recurrent keratouveitis and secondary glaucoma. We report a case of chronic recurrent anterior uveitis with secondary glaucoma presenting with acute visual loss and interface fluid 9 years after laser in situ keratomileusis. Based on clinical presentation, a viral aetiology was suspected. Aqueous tap was positive for CMV-DNA by real-time quantitative PCR of the aqueous humour. The patient was treated with systemic antivirals, topical corticosteroids and antiglaucoma medications. The interface fluid resorbed rapidly. The intraocular pressure (IOP) was controlled by trabeculectomy. There was no further corneal deterioration at 7-month follow-up and the IOP had also stabilised. We believe this is only the third reported case of CMV-related interface fluid syndrome. This case highlights the role of quantitative PCR analysis for establishing viral aetiology in recurrent unilateral hypertensive anterior uveitis and reports the unusual finding of interface fluid which resolved after starting systemic antiviral therapy. [ABSTRACT FROM AUTHOR]

Aims To first describe in vivo confocal microscopic (IVCM) corneal findings in severe dry eye syndrome due to ocular chronic graft versus host disease (cGvHD) after allogeneic stem cell transplantation. Methods IVCM of the central cornea was performed in 12 prospectively recruited patients with severe ocular cGvHD associated dry eye syndrome and in six control patients with haematological malignancies without cGvHD. Within each examined corneal layer, at least three non-overlapping areas were selected for representative analysis. Results The number of sub basal nerve branches was markedly reduced in patients with cGvHD. Sub basal nerve morphology was characterised by increased tortuosity and reduced reflectivity. Accumulation of hyper-reflective extracellular matrix, significantly increased haze and increased keratocyte density were found in the anterior stroma of the study group. Conclusions IVCM findings of the cornea in patients with severe ocular cGvHD include a rarefaction of the sub basal corneal nerve plexus and dense accumulation of hyper-reflective extracellular matrix in the anterior stroma. [ABSTRACT FROM AUTHOR]

Background/aims To investigate the clinical effectiveness of adjunctive triamcinolone acetonide (TA) given at the time of vitreoretinal surgery following open globe trauma (OGT). Methods A phase 3, multicentre, double-masked randomised controlled trial of patients undergoing vitrectomy following OGT comparing adjunctive TA (intravitreal and subtenons) against standard care (2014-2020). The primary outcome was the proportion of patients with at least 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letter improvement in corrected visual acuity (VA) at 6 months. Secondary outcomes included: change in ETDRS, retinal detachment (RD) secondary to PVR, retinal reattachment, macular reattachment, tractional RD, number of operations, hypotony, elevated intraocular pressure and quality of life. Results 280 patients were randomised over 75 months, of which 259 completed the study. 46.9% (n=61/130) of patients in the treatment group had a 10-letter improvement in VA compared with 43.4% (n=56/129) of the control group (difference 3.5% (95% CI -8.6% to 15.6%), OR=1.03 (95% CI 0.61 to 1.75), p=0.908)). Secondary outcome measures also failed to show any treatment benefit. For two of the secondary outcome measures, stable complete retinal and macular reattachment, outcomes were worse in the treatment group compared with controls, respectively, 51.6% (n=65/126) vs 64.2% (n=79/123), OR=0.59 (95% CI 0.36 to 0.99), and 54.0% (n=68/126) vs 66.7% (n=82/123), OR=0.59 (95% CI 0.35 to 0.98), for TA vs control. Conclusion The use of combined intraocular and sub-Tenons capsule TA is not recommended as an adjunct to vitrectomy surgery following OGT. [ABSTRACT FROM AUTHOR]

Background/aims To compare the influence of choroidal microvasculature dropout (cMvD) on progressive retinal nerve fibre layer (RNFL) thinning in glaucomatous eyes with parapapillary β-zones and γ-zones. Methods 294 eyes with primary open-angle glaucoma (POAG) and parapapillary atrophy (PPA) underwent optical coherence tomography (OCT) to determine the type of PPA and OCT angiography scanning of the optic nerve head to determine the presence of cMvD. Eyes were classified based on the type of PPA (β-zones and γ-zones), and their clinical characteristics were compared. Factors associated with the rate of rapid progressive RNFL thinning were determined in each group, including the presence of cMvD as an independent variable. Results Of the 294 eyes, 186 and 108 were classified as having β-zones and γ-zones, respectively. The rate of RNFL thinning was slower (p<0.001), axial length was longer (p<0.001) and presence of cMvD was less frequent (57.4% vs 73.1%, p=0.006) in eyes with γ-zone than those with β-zone. Multivariate analyses showed that greater lamina cribrosa curvature (p=0.047) and the presence of cMvD (p=0.010) were associated with a faster rate of RNFL thinning in eyes with β-zone, whereas larger intraocular pressure fluctuation (p<0.001), shorter axial length (p=0.042) and greater baseline RNFL thickness (p<0.001) were associated with a faster rate of RNFL thinning in eyes with γ-zone. Conclusions The presence of cMvD was significantly associated with a faster rate of RNFL thinning in POAG eyes with β-zone, but not γ-zone. The pathogenic consequences of cMvD in POAG eyes may depend on accompanying peripapillary structures. [ABSTRACT FROM AUTHOR]

Purpose Corneal biomechanical failure is the hallmark of keratoconus (KC); however, the cause of this failure remains elusive. Collagen type XII (COL12A1), which localises to Bowman's layer (BL), is thought to function in stress-bearing areas, such as BL. Given the putative protective role of COL12A1 in biomechanical stability, this study aims to characterise COL12A1 expression in all corneal layers involved in KC. Methods TaqMan quantitative PCR was performed on 31 corneal epithelium samples of progressive KC and myopic control eyes. Tissue microarrays were constructed using full-thickness corneas from 61 KC cases during keratoplasty and 18 non-KC autopsy eyes and stained with an antibody specific to COL12A1. Additionally, COL12A1 was knocked out in vitro in immortalised HEK293 cells. Results COL12A1 expression was reduced at transcript levels in KC epithelium compared with controls (ratio: 0.58, p<0.03). Immunohistochemical studies demonstrated that COL12A1 protein expression in BL was undetectable, with reduced expression in KC epithelium, basement membrane and stroma. Conclusions The apparent absence of COL12A1 in KC BL, together with the functional importance that COL12A1 is thought to have in stress bearing areas, suggests that COL12A1 may play a role in the pathogenesis of KC. Further studies are necessary to investigate the mechanisms that lead to COL12A1 dysregulation in KC. [ABSTRACT FROM AUTHOR]

Aim To describe in vivo confocal microscopy (IVCM) features of the limbus in normal eyes as related to the palisades of Vogt's. Methods 46 eyes of 29 consecutive volunteers were recruited in this observational study. A detailed examination by IVCM was performed in addition to a routine slit-lamp biomicroscopy. Size and density of corneal and limbal epithelial cells were measured and statistically analysed using SPSS version 8.0 software. Results Anatomical and morphological features were noted between corneal and limbal cells. Size and density differences reached to significant levels (p<0.05). Different shapes of palisades of Vogt have been described clearly by confocal microscope. Cell-like structures were observed in the peripheral end of the palisades which might represent limbal stem cell crypts. Conclusions Laser IVCM can be used to establish the features of the normal limbus. The identified features demonstrate quantitative changes in the basal epithelium between the limbus and the central cornea and morphological differences between pigmented or nonpigmented studied subjects. Further studies should be performed to correlate with histology the possible crypts which were observed in this study. [ABSTRACT FROM AUTHOR]

AIM: To evaluate, by impression cytology (IC), the cytological features of the central area of corneal epithelial surface of patients with symptomatic bullous keratopathy (BK). DESIGN: Cross-sectional observational case series. METHODS: IC of the central cornea was performed in 72 eyes of 72 patients with symptomatic BK between June 2005 and December 2006. Patients were divided into two groups according to the presence (group GC) or not of goblet cells (group NGC). The diagnosis of limbal stem cell deficiency (LSCD) was defined by the presence of one or more intact goblet cells on the corneal surface. Squamous metaplasia was classified according to Murube and Rivas. RESULTS: Epithelial squamous metaplasia was found in 72 (100%) eyes, along with conjunctival goblet cells in 25 (34.72%) eyes. Squamous metaplasia was grade 1 in group GC and more advanced grades in group NGC. Corneal neovascularisation was present in 62 (82.11%) eyes. Vessel measure was more than 4 mm in 11 eyes (23.4%) in group NGC and 10 eyes (40%) in group GC (p=0.559), and they were mostly subepithelial in 23 eyes (48.9%) in group NGC and 12 (48%) eyes in group GC (p=0.822). CONCLUSION: Squamous metaplasia was the most frequent finding associated with advanced BK. The presence of goblet cells on the surface of corneas with squamous metaplasia grade 1, in a significant number of patients, suggests that limbal stem cell deficiency is a common condition associated with advanced cases of BK. [ABSTRACT FROM AUTHOR]

AIMS: To evaluate the effect of topical autologous plasma on nerve morphology in patients with neurotrophic keratopathy (NK) using the confocal microscope. METHODS: Eleven eyes of six patients with neurotrophic keratopathy were evaluated for this study. Corneal fluorescein staining was done, and corneal sensitivity measurements were done with the Cochet–Bonnet and modified Belmonte gas aesthesiometers. The Heidelberg Retina Tomograph 2 Rostock Cornea Module laser scanning confocal microscope was used to image the corneal surface and subepithelial neural plexus. Four images at the level of the subepithelial nerve plexus in the central cornea were randomly selected for analysis of the corneal nerves. Topical autologous plasma was used six to eight times per day. RESULTS: The best-corrected visual acuity improved significantly after plasma treatment in all patients (p=0.003). The mean corneal fluorescein staining score significantly decreased after treatment (p=0.0003). There was a significant increase in corneal sensitivity measured by Cochet–Bonnet (p<0.0001) and modified Belmonte (p=0.01) aesthesiometers. The mean number, length, width and density of subepithelial nerves increased significantly after plasma treatment (p=0.0002). CONCLUSION: In vivo confocal microscopy examination revealed preliminary evidence for improvement of corneal nerve findings suggesting efficacy of autologous plasma treatment in neurotrophic keratopathy. [ABSTRACT FROM AUTHOR]

AIM: This study was performed to independently assess the turnover rates of aqueous and lipid layers of the tear film. METHODS: Two fluorescent dyes, fluorescein sodium and 5-dodecanoylaminofluorescein (DAF), which is a free-fatty-acid conjugate of fluorescein, were applied to the right eye of 12 healthy volunteers. Fluorescent intensity of the precorneal tear film was measured at the central cornea every minute for 10 min for fluorescein sodium, and every 5 min for 50 min for DAF. The turnover rate was calculated by plotting fluorescent intensity against time in a semilog plot and expressed as %/min. RESULTS: Turnover rates of fluorescein sodium and DAF were 10.3 (SD 3.7)%/min and 0.93 (0.36)%/min, respectively. The turnover rate of DAF was significantly lower than that of fluorescein sodium (p<0.05, Mann–Whitney test). The turnover rate of DAF positively correlated with that of fluorescein sodium (r = 0.93, p<0.05). CONCLUSION: Our results indicate that the turnover of lipids in tears is much slower than the aqueous flow of tears, and that this lipid turnover is associated with the aqueous flow of tears in healthy adults. [ABSTRACT FROM AUTHOR]

Aim: To quantify human corneal recovery after moderate to high myopic laser in situ keratomileusis (LASIK) in a 2-year prospective follow-up study. Methods: Fifteen eyes of 15 patients (mean refraction -10.1 (SD 2.4) D) were examined preoperatively and postoperatively at day 1, 5 days, 2 weeks, 1, 3 and 6 months and 2 years. Biomicroscopy, visual acuity and refraction were examined prior to imaging studies. An in vivo tandem scanning confocal microscope was used to obtain images from the central cornea. Subbasal nerve density was measured as the total length of nerve trunks in confocal image per mm[sup2]. Keratocyte density was calculated manually from stromal sublayers. The thickness of the altered keratocyte zone was measured on both sides of the LASIK interface. Results: At the end of the follow-up, all patients had a 20/20 BCVA, and nine of 15 patients were within ± 0.5 D of the intended correction. The total corneal thickness remained unaltered, but epithelial hyperplasia was seen at 2 years. Keratocyte density in the anterior stroma and posterior to the flap interface showed a slight decrease during the follow-up. Subbasal nerve density decreased 82% in 5 days after LASIK. A gradual increase was observed from 2 weeks postoperatively, but even 2 years after the operation the nerve density was only 64% from the preoperative values. Conclusions: Subbasal nerve fibre density shows a gradual recovery throughout the follow-up. However, only three subjects showed totally regenerated subbasal nerve fibres at 2 years. This may correlate with the observed decrease in the density of the most anterior keratocytes. Corneal remodelling seemed to continue for at least 2 years. [ABSTRACT FROM AUTHOR]

Purpose: This study was performed to separately assess the aqueous flow applied with hyaluronic acid, and the behaviour of hyaluronic acid itself on the ocular surface. Methods: Two different fluorescent dyes, fluorescein sodium dissolved in 0.1% hyaluronic acid (HA) solution and 0.1% fluorescein conjugated with hyaluronic acid (F-HA) dissolved in saline, were used. A volume of 20 µl of tested solution was applied to the eye of 10 healthy volunteers. Fluorescein sodium dissolved in saline served as a control. The fluorescent intensity of the precorneal tear film was measured at the central cornea every minute for 10 min. The turnover rate was calculated using the equation that plots fluorescent intensity against time in a semilog plot and expressed as %/min. Results: Turnover rates of topically applied 0.1% F-HA, 0.1% HA and saline were 8.1 (SD 3.6)%/min, 21.6 (2.8)%/min, and 31.0 (3.7)%/min, respectively. The turnover rate of F-HA was significantly lower than those of HA and saline (p = 0.00012 and p = 0.00000022, respectively; Mann-Whitney test). The turnover rate of HA was significantly lower than that of. saline (p = 0.00001; Mann-Whitney test). Conclusion: Our results indicate that the bulk aqueous flow applied with HA and the turnover of HA itself are different. HA molecules may adhere to the ocular surface by surface-chemical and/or biochemical properties. The long retention time of HA on the ocular surface may explain the mechanism in which hyaluronic acid has been shown to enhance tear film stability for a few hours. [ABSTRACT FROM AUTHOR]

Aims: To determine the repeatability of ocular surface sensitivity to mechanical stimulation using air stimuli and the effect of contact lens (CL) wear on sensitivity. Methods: Repeatabiliiy 14 subiects (24-39 years) participated. Mechanical sensitivity to warmed (34°C) and ambient (20°C) air was measured for the central cornea (CC), inferior cornea (IC), and inferior con junctiva (ICON). Measurements were taken on 12 days; six morning and six afternoon measurements. Differences between sites, time of day, and stimulus temperature were evaluated. CL wear 10 subjects (22-30 years) participated. Measurements were taken at the same time of day, either following no wear, wear of a CL of oxygen permeability [DkJ of 28 × 10-9 [cm/s][ml O2/ml mm Hg] or wear of a CL of Dk 140 × 10-9 [cm/sj[mi O2/ml mm Hg]. Differences between sites and wear conditions were evaluated. Results: Repeatability: Sensitivity varied between sites (p< 10-90.01), time of day (p<0.05), and stimulus temperatures (p<0.01). There were no significant differences between days. Mean thresholds For eye temperature stimuli were; CC 64.4 (SD 28.6) mI/mm; IC 84.6(40.0) ml/min; 1CON 120.6(40.4) mi/mm and for ambient temperature stimuli were CC 53.9 (16.0) mi/mm, IC 59.0 (20.0) mI/mm; ICON 72.6 (43.7) mI/mm. CL wear Sensitivity varied between sites and wear conditions (p<0.05). Conjunctival sensitivity was increased after wear of highly oxygen permeable CLs but unaffected by wear of low oxygen permeable CLs. Conclusions: The prototype gas aesthesiometer is able to repeatably measure ocular surface sensitivity and measurements are consistent with previously reported techniques. [ABSTRACT FROM AUTHOR]

Aim To evaluate changes in the ocular surface and tear film with age and mutational status in congenital aniridia. Methods 45 participants with congenital aniridia (89 eyes) in a prospective, cross-sectional study. Whole-exome sequencing identified the causative mutation. Examinations included slit-lamp biomicroscopy, in vivo confocal microscopy, Ocular Surface Disease Index (OSDI) score, blink rate, Schirmer I test, Oxford Staining Score (OSS), tear film break-up time (TFBUT) and Ocular Protection Index (OPI). Results There were age-dependent increases in OSDI (β=0.34, 95% CI 0.03 to 0.66; p=0.030), blink rate (β=0.18, 95% CI 0.08 to 0.27; p<0.001) and OSS (β=0.05, 95% CI 0.03 to 0.07; p<0.001) and age-dependent reductions in tear production (β=-0.23, 95% CI -0.43 to 0.02; p=0.029) and TFBUT (β=-0.10, 95% CI -0.17 to -0.04; p<0.001). Perturbed OSDI, OSS, blink rate, tear production and TFBUT were noted after the age of ten and OSDI, OSS, blink rate and TFBUT correlated with deficient corneal nerves and limbal stem cell function. OSDI, blink rate, Schirmer, OSS, TFBUT and OPI were not associated with type of PAX6 mutation, but OSDI, OSS and blink rate associated with grade of aniridia-associated keratopathy. Conclusions Ocular surface damage and dry eye signs appear in congenital aniridia regardless of mutation, appearing after 10 years of age and progressing thereafter. An early treatment window may exist for therapies to protect the ocular surface homoeostasis and limbal function, to possibly delay keratopathy development and progression. [ABSTRACT FROM AUTHOR]

Aim To propose a new scoring system in the assessment of ocular surface epithelial damage in vernal keratoconjunctivitis (VKC). Methods 25 consecutive patients with VKC (50 eyes) were evaluated using the Quality of Life in children with VKC (QUICK) questionnaire and objective clinical measures: fluorescein and lissamine green staining and cornea confocal microscopy (Heidelberg Retina Tomography 3). Oxford, Van Bljsterweld and a new system, the VKC-Collaborative Longitudinal Evaluation of Keratoconus study (CLEK) (VKC-CLEK) scores, were used to evaluate the epithelial damage after staining. Results Mean Oxford and VKC-CLEK scores were significantly different after fluorescein staining (P<0.001), but significantly correlated (P<0.001; r=0.649). The same data were obtained comparing Van Bljsterweld and VKC-CLEK after lissamine green staining (P<0.001; r=0.760). In patient with limbal VKC, a statistically significant difference was found comparing new VKC-CLEK scores and Oxford or Van Bljsterweld scores (P<0.001), but not in tarsal VKC. A statistically superior concordance was found between QUICK and VKC-CLEK scores compared with standard staining scores values (P<0.001). Conclusions Oxford and Van Bijsterveld scores are not adequate for the evaluation of the epithelial damage in patients with limbal VKC because the staining patterns considered for these tests do not correspond to the staining patterns in patients with VKC. We propose a new scoring system, VKC-CLEK, to better evaluate both limbal and tarsal epithelial damage in patients with VKC. [ABSTRACT FROM AUTHOR]

Purpose Archipelago keratitis (ApK) is a subtype of Herpesviridae stromal keratitis that consists of subepithelial nummular inflammatory infiltrates arranged in a radial centripetal pattern. This rare and poorly described form is not often recognised early. We report the first large series of ApK, with an analysis of clinical settings at presentation, evolution of the disease with time and a description of factors associated with recurrence. Methods The clinical records of 82 patients (83 eyes) with a diagnosis of ApK between 2011 and 2021 in two centres were reviewed. Results The median age of the 82 patients at referral was 37±28 years. ApK was unilateral in all but one case. A total of 76% of patients had at least one second diagnostic criteria suggesting a herpetic aetiology. Overall, 44 (53%) eyes exhibited least one recurrence after a median of 12 months. Recurrence was frequently associated with neovascularisation (HR 2.1, 95% CI 1.1 to 3.9; p=0.02) and tapering corticosteroids (HR 3.5, 95% CI 1.8 to 7.1; p<0.01) or valaciclovir use (HR=2.3, 95% CI 1.2 to 4.6; p=0.01). Antiviral treatment was used in all patients, whereas local anti-inflammatory drugs such as corticosteroids and/or ciclosporin were used in 73 (88%) cases. Conclusion ApK is a Herpesviridae stromal keratitis that is typically unilateral in presentation and features a high risk of recurrence. Combined treatment with antiviral and anti-inflammatory drugs are usually required over the long term. Topical ciclosporin can be useful as a corticosteroid-sparing treatment. [ABSTRACT FROM AUTHOR]

A male patient in his 30s, with a history of bilateral microkeratome-assisted myopic laser-assisted in situ keratomileusis (LASIK) 8 years ago at another centre, presented to us with gradually progressive diminution of vision and glare in both eyes for the last 4 years. On presentation, uncorrected distance visual acuity (UDVA) was 6/24 and 6/15 in the right eye and left eye, respectively, with normal intraocular pressures. Slit-lamp examination and anterior segment optical coherence tomography revealed well-defined white deposits, limited to an area within the LASIK flap. The deposits were confluent, at the level of the LASIK flap interface, and few discrete opacities were present in the posterior stroma. His father also had a similar clinical picture in both eyes. A diagnosis of both eyes post-LASIK exacerbation of granular corneal dystrophy with epithelial ingrowth was made. He underwent right eye femtosecond laser-assisted sutureless superficial anterior lamellar keratoplasty. At 6-month follow-up, UDVA improved to 6/12 with graft clarity of 4+ and coexistent grade 1 epithelial ingrowth. [ABSTRACT FROM AUTHOR]

Aims To report the baseline intraocular pressure (IOP) characteristics and its diurnal fluctuation in the Laser in Glaucoma and Ocular Hypertension China cohort. Methods 622 primary open-angle glaucoma (POAG) patients and 149 ocular hypertension (OHT) patients were recruited at Zhongshan Ophthalmic Center from 2015 to 2019. Standardised ocular examinations were performed including IOP measurement using the Goldmann applanation tonometer. Daytime phasing IOP was recorded at 8:00, 10:00, 11:30, 14:30, 17:00 hour. Results The mean baseline IOP was 20.2 mm Hg for POAG patients and 24.4 mm Hg for OHT. Multiple regression analysis revealed that thicker central corneal thickness (CCT) was correlated with higher IOP in both POAG and OHT. Male gender and younger age were correlated with higher IOP only for POAG. As for diurnal IOP fluctuation, mean IOP fluctuation was 3.4 mm Hg in POAG eyes and 4.4 mm Hg in OHT. The peak and trough IOP occurred at 8:00 and 14:30 hour in both POAG and OHT eyes. Conclusions Younger age, male gender and thicker CCT are correlated to higher IOP in POAG patients while only thicker CCT is related to higher IOP in OHT patients. Peak IOP appears mostly at early morning or late afternoon and trough value occurs mostly at early afternoon. [ABSTRACT FROM AUTHOR]

Purpose To study the outcome of a modified amnion-assisted conjunctival epithelial redirection (ACER) technique using vacuum-dried amnion (Omnigen) and fibrin glue for managing total limbal stem cell deficiency (LSCD). Method A retrospective, interventional case series of all patients with total LSCD who underwent limbal stem cell transplant (LSCT) using the modified ACER procedure between 2016 and 2019. The outcome was defined as: (1) success: complete corneal re-epithelialisation without conjunctivalisation; (2) partial success: sub-total corneal re-epithelialisation with partial non-progressive conjunctivalisation sparing the visual axis and (3) failure: conjunctivalisation affecting the visual axis. Results Ten patients (six men), with a mean age of 46.2±18.4 years, were included. The mean follow-up was 23.0±13.9 months. Causes of LSCD were chemical eye injury (30%), congenital aniridia-related keratopathy (30%), ocular surface malignancy (20%), Steven-Johnson syndrome (10%) and contact lens overuse (10%). 50% were bilateral. The time from diagnosis to ACER (for acquired causes) was 45.6±44.4 months. 80% of patients achieved a complete/partial success following ACER and 20% of patients required repeat LSCT. Auto-LSCT was associated with a significantly higher chance of success than allo-LSCT (p=0.048). The mean best-corrected-visual-acuity (logMAR) improved significantly from 1.76±0.64 preoperatively to 0.94±0.94 at final follow-up (p=0.009). Omnigen was available off-the-shelf stored at room temperature and its transparency enabled visualisation of the healing epithelium beneath. Conclusion LSCT using the modified ACER serves as an effective ocular surface reconstruction technique in managing total LSCD and improving vision. Vacuum-dried amnion provides advantages of easy handling, transparency and storage at room temperature. [ABSTRACT FROM AUTHOR]

Background The combination of topical interferon α-2b (IFN α-2b) and all-trans retinoic acid (ATRA) 0.01% has previously been shown to be effective in conjunctival and corneal intraepithelial neoplasia. This combination was incidentally found to be effective in a patient with partial limbal stem cell deficiency (LSCD), a condition which can be challenging to treat if conservative measures fail. This retrospective study evaluates the combination of topical IFN α-2b and ATRA 0.01% in the treatment of partial LSCD. Methods Five patients from one institution with a clinical and/or histopathological diagnosis of LSCD had failed a period of conservative treatment with cessation of toxic stimuli and use of lubricating eye-drops. These patients were treated with a combination regimen of topical IFN α-2b and ATRA 0.01%. Results All five patients had partial LSCD, but limbal involvement was significantly worse in one patient who later progressed to total LSCD. Complete clinical resolution of signs of LSCD was achieved in the four patients with partial LSCD after a mean of 9 months of treatment. The one patient who progressed to total LSCD did not respond to treatment. Duration of follow-up after clinical resolution in the four patients with partial LSCD was at least 18 months, with no signs of recurrence seen. Aside from the complaint of ocular irritation in one patient, no other side effects were observed. Conclusions Combination treatment of topical IFN α-2b and ATRA 0.01% can be considered in partial LSCD, where adjacent parts of the limbus remain intact. This treatment is associated with minimal side effects and no recurrence of signs of LSCD at least 18 months after clinical resolution. [ABSTRACT FROM AUTHOR]

We present a case of bilateral interstitial keratitis leading to perforation in a woman with hidradenitis suppurativa (HS). A woman in her mid-20s with a history of HS and Grave’s disease was referred to the corneal service with loss of vision and pain in both eyes since childhood. She was found to have circumferential thinning and steepening affecting her peripheral cornea bilaterally. Corrected distance visual acuity with spectacles was in the right eye 6/7.5, and in the left 6/30, with local thinnest area of 209 and 217 μm in the right and left eyes, respectively. She experienced recurring episodes of redness and irritation, and perforation occurred. The corneal perforation was managed with cyanoacrylate glueing, followed by a local conjunctival flap. Systemic immunosuppression with mycophenolate mofetil and adalimumab was commenced, with improvement after 18 months of treatment. Dermatologists and ophthalmologists should be aware of this association given its potential severity. [ABSTRACT FROM AUTHOR]

Aims To identify risk factors for rebubbling, and early graft failure after Descemet membrane endothelial keratoplasty (DMEK). Methods In this prospective registry study, all consecutive DMEK procedures registered in the Netherlands Organ Transplant Registry were assessed (n=752). Univariable and multivariable analysis was performed using logistic regression. The effect of rebubbling on endothelial cell density was analysed using a linear mixed model. Results 144 of 752 (19%) eyes underwent rebubbling. Rebubbling was successful in 101 eyes (70%). In eyes that underwent rebubbling, the graft failure rate was significantly higher than eyes that did not undergo rebubbling (30% vs 9%, respectively; OR: 4.28, 95% CI 2.72 to 6.73, p<0.001). In multivariable analysis, independent risk factors for rebubbling were surgical complication (OR: 2.28, 95% CI 1.20 to 4.33, p=0.012) and older recipient age (OR: 1.04 (per increase of 1 year), 95% CI 1.01 to 1.07, p=0.003). Risk factors for developing graft failure within 3 months were transplant before 2016 (OR: 3.32, 95% CI 1.87 to 5.90, p<0.001), and surgical complication (OR: 2.93, 95% CI 1.42 to 6.04, p=0.004). Throughout the study period, rebubbling and early graft failure were inversely related. Eyes that underwent rebubbling showed significantly lower endothelial cell densities at 3, 6 and 12 months compared with eyes that did not undergo rebubbling (all p<0.001). Conclusions This Dutch registry study identified independent risk factors for DMEK graft detachment leading to rebubbling, namely recipient age and surgical complication, and early graft failure, namely transplantation before 2016 and surgical complication. Rebubbling was associated with significantly higher endothelial cell loss in the first year after surgery. [ABSTRACT FROM AUTHOR]

Background/aims To evaluate the performances of deep learning (DL) algorithms for detection of presence and extent pterygium, based on colour anterior segment photographs (ASPs) taken from slit-lamp and hand-held cameras. Methods Referable pterygium was defined as having extension towards the cornea from the limbus of >2.50 mm or base width at the limbus of >5.00 mm. 2503 images from the Singapore Epidemiology of Eye Diseases (SEED) study were used as the development set. Algorithms were validated on an internal set from the SEED cohort (629 images (55.3% pterygium, 8.4% referable pterygium)), and tested on two external clinic-based sets (set 1 with 2610 images (2.8% pterygium, 0.7% referable pterygium, from slit-lamp ASP); and set 2 with 3701 images, 2.5% pterygium, 0.9% referable pterygium, from hand-held ASP). Results The algorithm's area under the receiver operating characteristic curve (AUROC) for detection of any pterygium was 99.5%(sensitivity=98.6%; specificity=99.0%) in internal test set, 99.1% (sensitivity=95.9%, specificity=98.5%) in external test set 1 and 99.7% (sensitivity=100.0%; specificity=88.3%) in external test set 2. For referable pterygium, the algorithm's AUROC was 98.5% (sensitivity=94.0%; specificity=95.3%) in internal test set, 99.7% (sensitivity=87.2%; specificity=99.4%) in external set 1 and 99.0% (sensitivity=94.3%; specificity=98.0%) in external set 2. Conclusion DL algorithms based on ASPs can detect presence of and referable-level pterygium with optimal sensitivity and specificity. These algorithms, particularly if used with a handheld camera, may potentially be used as a simple screening tool for detection of referable pterygium. Further validation in community setting is warranted. Synopsis/precis DL algorithms based on ASPs can detect presence of and referable-level pterygium optimally, and may be used as a simple screening tool for the detection of referable pterygium in community screenings. [ABSTRACT FROM AUTHOR]

Background/Aims Long COVID is characterised by a range of potentially debilitating symptoms which develop in at least 10% of people who have recovered from acute SARS-CoV-2 infection. This study has quantified corneal sub-basal nerve plexus morphology and dendritic cell (DC) density in patients with and without long COVID. Methods Forty subjects who had recovered from COVID-19 and 30 control participants were included in this cross-sectional comparative study undertaken at a university hospital. All patients underwent assessment with the National Institute for Health and Care Excellence (NICE) long COVID, Douleur Neuropathique 4 (DN4) and Fibromyalgia questionnaires, and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), corneal nerve fibre length (CNFL), and total, mature and immature DC density. Results The mean time after the diagnosis of COVID-19 was 3.7±1.5 months. Patients with neurological symptoms 4 weeks after acute COVID-19 had a lower CNFD (p=0.032), CNBD (p=0.020), and CNFL (p=0.012), and increased DC density (p=0.046) compared with controls, while patients without neurological symptoms had comparable corneal nerve parameters, but increased DC density (p=0.003). There were significant correlations between the total score on the NICE long COVID questionnaire at 4 and 12 weeks with CNFD (ρ=-0.436; p=0.005, ρ=-0.387; p=0.038, respectively) and CNFL (ρ=-0.404; p=0.010, ρ=-0.412; p=0.026, respectively). Conclusion Corneal confocal microscopy identifies corneal small nerve fibre loss and increased DCs in patients with long COVID, especially those with neurological symptoms. CCM could be used to objectively identify patients with long COVID. [ABSTRACT FROM AUTHOR]

A 20-year-woman with bilateral keratoconus developed acute hydrops of her right cornea. The amount of corneal oedema progressively increased over eight weeks while the central cornea thinned. Histologically the cornea contained a stromal pseudocyst that was in continuity with the anterior chamber through breaks in Descemet's membrane. Pseudocyst formation is a rare complication of acute corneal hydrops that can simulate severe corneal ectasia. [ABSTRACT FROM PUBLISHER]

Purpose To assess whether alterations in stromal keratocyte density are related to loss of corneal nerve fibres in children with type 1 diabetes mellitus (T1DM). Methods Twenty participants with T1DM and 20 age-matched healthy controls underwent corneal confocal microscopy. Corneal sub-basal nerve morphology and corneal keratocyte density (KD) were quantified. Results Corneal nerve fibre density (CNFD) (p<0.001), corneal nerve branch density (p<0.001), corneal nerve fibre length (CNFL) (p<0.001) and inferior whorl length (IWL) (p<0.001) were lower in children with T1DM compared with healthy controls. Anterior (p<0.03) and mid (p=0.03) stromal KDs were lower with no difference in posterior KD (PKD) in children with T1DM compared with controls. Age, duration of diabetes, height, weight and body mass index did not correlate with anterior (AKD), mid (MKD) or PKD. Inverse correlations were found between glycated haemoglobin and PKD (r=-0.539, p=0.026), bilirubin with MKD (r=-0.540, p=0.025) and PKD (r=-0.531, p=0.028) and 25-hydroxycholecalciferol with MKD (r=-0.583, p=0.018). CNFD, CNFL and IWL did not correlate with AKD, MKD or PKD. Conclusion This study demonstrates a reduction in corneal nerves and anterior and mid stromal KD in children with T1DM, but no correlation between corneal nerve and keratocyte cell loss. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to evaluate the incidence, timing and risk factors of corneal neovascularisation (NV) after deep anterior lamellar keratoplasty (DALK) for corneal ectasia. Methods This study included 616 eyes who underwent DALK between 2012 and 2020 in two tertiary referral centres. In one centre topical corticosteroids were discontinued after complete suture removal 1 year after surgery, whereas in the other they were discontinued 3-4 months after surgery. The presence and severity of corneal NV was ascertained based on slit lamp photographs. Potential risk factors for corneal NV were evaluated using the Cox proportional hazards model. Results The cumulative incidence of corneal NV was 8.7% at 1 year after surgery and 13.2% at 5 years. Mean time interval from surgery to development of corneal NV was 12.8±16.2 months, with 68.9% of cases occurring before complete suture removal. Early discontinuation of topical steroids, older age and ocular allergy were associated with an increased risk of developing corneal NV (respectively, HR=2.625, HR=1.019, HR=3.726, all p<0.05). Conclusions The risk of corneal NV is higher in the first year following DALK. Early discontinuation of topical steroids, ocular allergy and older age are significant predictors of corneal NV. [ABSTRACT FROM AUTHOR]

Background/aims This study aimed to predict the possibility of steroid-induced ocular hypertension (OHT) after intravitreal dexamethasone (DEX) implantation and to identify a proper safety zone for such injections. Methods A cross-sectional observational study was conducted and included 908 patient eyes that underwent DEX implant injection due to various retinal diseases. Intraocular pressure (IOP) was measured before injection, at 1 week, and at 1, 2, 3, 6 and 12 months thereafter. Eyes of enrolled patients were divided into the OHT and normal IOP groups. Univariable logistic regression analysis was used to assess significant associations between steroid-induced OHT and covariates; significant and previously reported significant variables were analysed with a multivariable model, and predictive nomograms were developed. Results Age, sex, axial length, glaucomatous eye, neovascular glaucoma, secondary glaucoma, uveitis history, hypertension, depression, diabetes mellitus and a history of previous laser-assisted in-situ keratomileusis or laser-assisted subepithelial keratectomy were significantly related to steroid-induced OHT (p<0.05). The calibration plot revealed good prediction under a predicted value of 0.4. Cut-off values for 80%, 86%, 91%, 95% and 98% sensitivity and specificity were offered for the safety zone after intravitreal DEX implantation. Conclusion We developed two nomograms to predict a safety zone for intravitreal DEX implantation. These can be used to identify individuals who may be safely prescribed steroid treatments and for whom extra caution should be exercised. [ABSTRACT FROM AUTHOR]

Aim To evaluate and compare early corneal wound healing and inflammatory responses after small incision lenticule extraction (SMILE) versus femtosecond laser laser in situ keratomileusis (LASIK). Methods Thirty-six eyes of 36 rabbits underwent SMILE, while another 36 eyes of 36 rabbits were treated with femtosecond laser LASIK. All the eyes were subjected to the same refractive correction of -6.00 DS/-1.00 DC. Twelve eyes that had no surgery were included for control. After euthanisation, corneal tissue sections were evaluated with terminal deoxyribonucleotidyl transferasemediated dUTP-digoxigenin nick-end labelling (TUNEL) assay to detect apoptosis at postoperative 4 and 24 h, immunocytochemistry for Ki67 to detect keratocyte proliferation at postoperative day 3, week 1 and month 1, and immunocytochemistry for CD11b to detect inflammation at postoperative day 1, day 3 and week 1, respectively. Results No adverse effects were noted after SMILE or LASIK. Corneal healing postoperatively was uneventful in all cases. There were significantly fewer TUNEL-positive corneal stromal cells after the SMILE procedure at 4 and 24 h postoperatively ( p<0.01) compared with the LASIK procedure. In addition, immunocytochemistry showed significantly fewer Ki67-positive cells in the SMILE group than those in the femtosecond laser LASIK group at day 3 and week 1 postoperatively ( p<0.05), but there was little expression of Ki67 at month 1 postoperatively in both groups. The CD11b-positive cells were significantly fewer in the SMILE group at day 1, day 3 and week 1 postoperatively ( p<0.01). Conclusions SMILE induces less keratocyte apoptosis, proliferation and inflammation compared with femtosecond laser LASIK. [ABSTRACT FROM AUTHOR]

An adult male in his 50s presented with complaints of glare and gradual, painless, progressive diminution of vision in the right eye (RE). Visual acuity in RE was noted to be 2/60, and slit lamp biomicroscopy revealed a pearly grey-white elevated corneal opacity measuring 4 mm × 3 mm, obscuring the visual axis. There was no history of ocular trauma or infection. The patient had undergone bilateral radial keratotomy for myopia correction 25 years ago. Anterior segment optical coherence tomography imaging demonstrated increased corneal thickness of 1080 µm at the site of lesion and the height of the epicorneal mass was noted to be 493 µm. The patient underwent fibrin glue-aided anterior lamellar keratoplasty. Histopathological examination of the excised host tissue confirmed the diagnosis of corneal keloid. [ABSTRACT FROM AUTHOR]

A man in his 30s, with a history of two operated penetrating keratoplasty (PK), primarily for viral keratitis, presented with pain, redness and diminution of vision in his left eye of 4 days duration. Postoperatively, he was prescribed oral antivirals, topical steroid eyedrops, lubricants and antiglaucoma medications. Eight months after transplantation, an epithelial defect with heaped up margins was noted on anterior segment evaluation on a routine follow-up visit. On checking his medications, it was found that the patient was unknowingly using bromfenac drops in place of brimonidine tartrate for the past month. A diagnosis of neurotrophic keratitis was made in the setting of PK performed for viral keratitis, incited by use of topical bromfenac. The patient was prescribed preservative-free lubricants with immediate discontinuation of bromfenac drops. Topical steroid drops were withheld till the epithelial defect healed. Complete healing of the defect was noted after 4weeks of therapy. [ABSTRACT FROM AUTHOR]

Background/aims This systematic review critically evaluated peer-reviewed publications describing morphological features consistent with, or using terms related to, a 'neuroma' or 'microneuroma' in the human cornea using laser-scanning in vivo confocal microscopy (IVCM). Methods The review was prospectively registered on PROSPERO (CRD42020160038). Comprehensive literature searches were performed in Ovid MEDLINE, Ovid Embase and the Cochrane Library in November 2019. The review included primary research studies and reviews that described laser-scanning IVCM for examining human corneal nerves. Papers had to include at least one of a pre-specified set of keyword stems, broadly related to neuromas and microneuromas, to describe a corneal nerve feature. Results Twenty-five papers (20 original studies; 5 reviews) were eligible. Three original studies evaluated corneal nerve features in healthy eyes. Most papers assessed corneal nerves in ocular and systemic conditions; seven studies did not include a control/comparator group. There was overlap in terminology used to describe nerve features in healthy and diseased corneas (eg, bulb-like/bulbous, penetration, end/s/ing). Inspection of IVCM images within the papers revealed that features termed 'neuromas' and 'microneuromas' could potentially be physiological corneal stromal-epithelial nerve penetration sites. We identified inconsistent definitions for terms, and limitations in IVCM image acquisition, sampling and/or reporting that may introduce bias and lead to inaccurate representation of physiological nerve characteristics as pathological. Conclusion These findings identify a need for consistent nomenclature and definitions, and rigorous IVCM scanning and analysis protocols to clarify the prevalence of physiological, as opposed to pathological, corneal nerve features. [ABSTRACT FROM AUTHOR]