Effects of Different Capsulotomy and Fragmentation Energy Levels on the Generation of Oxidative Stress Following Femtosecond Laser-Assisted Cataract Surgery.

PURPOSE: This study was conducted to evaluate the effects of different capsulotomy and fragmentation energy levels on the production of oxidative free radicals following femtosecond laser-assisted cataract surgery (FLACS) with a low-energy platform. METHODS: The experimental study included 60 porcine eyes (12 groups). In each group, capsulotomies with 90% or 150% energy, and fragmentations with 90%, 100%, or 150% energy or 150% with high spot density, respectively, were performed. Control samples were obtained from non-lasered eyes at the beginning (five eyes) and end (five eyes) of the experiment. In the clinical study, 104 eyes were divided into 5 groups, and they received conventional phacoemulsification (20 eyes), FLACS with 90% capsulotomy and 100% fragmentation energy levels without NSAIDs (16 eyes), FLACS with 90% (26 eyes) or 150% (22 eyes) capsulotomy energy levels, respectively, with a 100% fragmentation energy level and NSAIDs, and FLACS with 90% capsulotomy and 150% fragmentation energy levels and NSAIDs (20 eyes). Aqueous samples were analyzed for their malondialdehyde (MDA) and superoxide dismutase (SOD) levels. RESULTS: In the experimental study, there were no significant differences in the MDA and SOD levels between the groups with different capsulotomy energy levels. An increase in the fragmentation energy from 100% to 150% led to significantly higher MDA levels in the groups with both 90% (p = 0.04) and 150% capsulotomy energy levels (p = 0.03), respectively. However, increased laser spot densities did not result in significant changes in MDA or SOD levels. In the clinical study, all four of the FLACS groups showed higher MDA levels than the conventional group. Similarly, the increase in the fragmentation energy from 100% to 150% resulted in significantly elevated levels of MDA and SOD, respectively. CONCLUSIONS: Although increasing the FSL capsulotomy energy level may not have increased free radicals, higher fragmentation energy levels increased the generation of aqueous free radicals. However, fragmentation with high spot density did not generate additional oxidative stress. Increased spot density did not generate additional oxidative stress, and this can be helpful for dense cataracts.

Neuropathic Corneal Pain: Tear Proteomic and Neuromediator Profiles, Imaging Features, and Clinical Manifestations.

PURPOSE: To investigate the tear proteomic and neuromediator profiles, in vivo confocal microscopy (IVCM) imaging features, and clinical manifestations in neuropathic corneal pain (NCP) patients. DESIGN: Cross-sectional study. METHODS: A total of 20 NCP patients and 20 age-matched controls were recruited. All subjects were evaluated by corneal sensitivity, Schirmer test, tear break-up time, and corneal and ocular surface staining, Ocular Surface Disease Index and Ocular Pain Assessment Survey questionnaires were administered, as well as IVCM examinations for corneal nerves, microneruomas, and epithelial and dendritic cells. Tears were collected for neuromediator and proteomic analysis using enzyme-linked immunosorbent assay and data-independent acquisition mass spectrometry. RESULTS: Burning and sensitivity to light were the 2 most common symptoms in NCP. A total of 188 significantly dysregulated proteins, such as elevated metallothionein-2, creatine kinases B-type, vesicle-associated membrane protein 2, neurofilament light polypeptide, and myelin basic protein, were identified in the NCP patients. The top 10 dysregulated biological pathways in NCP include neurotoxicity, axonal signaling, wound healing, neutrophil degradation, apoptosis, thrombin signaling mitochondrial dysfunction, and RHOGDI and P70S6K signaling pathways. Compared to controls, the NCP cohort presented with significantly decreased corneal sensitivity (P < .001), decreased corneal nerve fiber length (P = .003), corneal nerve fiber density (P = .006), and nerve fiber fractal dimension (P = .033), as well as increased corneal nerve fiber width (P = .002), increased length, total area and perimeter of microneuromas (P < .001, P < .001, P = .019), smaller corneal epithelial size (P = .017), and higher nerve growth factor level in tears (P = .006). CONCLUSIONS: These clinical manifestations, imaging features, and molecular characterizations would contribute to the diagnostics and potential therapeutic targets for NCP.

Surgical Technique to Treat Presbyopic Inlay-Associated Corneal Haze With Sequential Excimer Photoablation: A Case Series.

PURPOSE: To describe an approach using sequential excimer laser ablation of the stromal surface of the corneal flap with or without subsequent excimer ablation to the stromal bed to reduce presbyopic inlay-associated corneal haze. METHODS: Twelve patients who underwent KAMRA inlay (Acufocus) explantation due to corneal haze were included. The mean interval between explantation and the primary surgery (phototherapeutic keratotomy [PTK] to corneal flap) was 16.2 ± 29.7 months (range = 1 to 83 months). The corneal flap was lifted and laid on an evisceration spoon and an excimer laser was used to ablate the flap stroma by 30 to 40 µm depth. Subsequently, an excimer laser was used to ablate and treat the stromal bed following a second flap lift according to the manifest refraction, leaving a minimal residual stromal bed thickness of greater than 300 µm. For both procedures, mitomycin C 0.02% was applied to the stromal bed before the flap was replaced and a bandage contact lens applied. RESULTS: Reductions in corneal haze were observed, following PTK to the corneal flap with or without photorefractive keratectomy (PRK) to the stromal bed, both clinically and on imaging. No significant changes in uncorrected distance visual acuity (P = .442) and corrected distance visual acuity (P = .565) were observed. Improvements were observed for both spherical equivalent refractive errors (P = .036) and corneal light backscatter (P = .019). There were significant improvements in spherical aberrations (P = .014) but no changes in total lower and higher order aberrations. CONCLUSIONS: PTK to the corneal flap with or without subsequent stromal bed PRK is an effective technique in treating corneal haze following presbyopic inlay explantation. [J Refract Surg. 2023;39(9):639-646.].

Mesenchymal Stem Cell Exosomes as Immunomodulatory Therapy for Corneal Scarring.

Corneal scarring is a leading cause of worldwide blindness. Human mesenchymal stem cells (MSC) have been reported to promote corneal wound healing through secreted exosomes. This study investigated the wound healing and immunomodulatory effects of MSC-derived exosomes (MSC-exo) in corneal injury through an established rat model of corneal scarring. After induction of corneal scarring by irregular phototherapeutic keratectomy (irrPTK), MSC exosome preparations (MSC-exo) or PBS vehicle as controls were applied to the injured rat corneas for five days. The animals were assessed for corneal clarity using a validated slit-lamp haze grading score. Stromal haze intensity was quantified using in-vivo confocal microscopy imaging. Corneal vascularization, fibrosis, variations in macrophage phenotypes, and inflammatory cytokines were evaluated using immunohistochemistry techniques and enzyme-linked immunosorbent assays (ELISA) of the excised corneas. Compared to the PBS control group, MSC-exo treatment group had faster epithelial wound closure (0.041), lower corneal haze score (p = 0.002), and reduced haze intensity (p = 0.004) throughout the follow-up period. Attenuation of corneal vascularisation based on CD31 and LYVE-1 staining and reduced fibrosis as measured by fibronectin and collagen 3A1 staining was also observed in the MSC-exo group. MSC-exo treated corneas also displayed a regenerative immune phenotype characterized by a higher infiltration of CD163+, CD206+ M2 macrophages over CD80+, CD86+ M1 macrophages (p = 0.023), reduced levels of pro-inflammatory IL-1ß, IL-8, and TNF-α, and increased levels of anti-inflammatory IL-10. In conclusion, topical MSC-exo could alleviate corneal insults by promoting wound closure and reducing scar development, possibly through anti-angiogenesis and immunomodulation towards a regenerative and anti-inflammatory phenotype.

Atypical microbial keratitis.

Atypical microbial keratitis refers to corneal infections caused by micro-organisms not commonly encountered in clinical practice. Unlike infections caused by common bacteria, cases of atypical microbial keratitis are often associated with worse clinical outcomes and visual prognosis. This is due to the challenges in the identification of causative organisms with standard diagnostic techniques, resulting in delays in the initiation of appropriate therapies. Furthermore, due to the comparatively lower incidence of atypical microbial keratitis, there is limited literature on effective management strategies for some of these difficult to manage corneal infections. This review highlights the current management and available evidence of atypical microbial keratitis, focusing on atypical mycobacteria keratitis, nocardia keratitis, achromobacter keratitis, and pythium keratitis. It will also describe the management of two uncommonly encountered conditions, infectious crystalline keratopathy and post-refractive infectious keratitis. This review can be used as a guide for clinicians managing patients with such challenging corneal infections.

The Effects of High Energy Capsulotomy on Aqueous Cytokine Profiles and Pupil Size During Femtosecond Laser-Assisted Cataract Surgery.

PURPOSE: To assess whether aqueous cytokine profiles and pupil size are altered when high capsulotomy energy is used in eyes undergoing femtosecond laser-assisted cataract surgery (FLACS), and if preoperative use of a topical non-steroidal anti-inflammatory drug (NSAID) has an effect on this. METHODS: This prospective study recruited 83 eyes (63 patients) that were allocated to four treatment groups: conventional phacoemulsification (n = 20 eyes); FLACS with 90% capsulotomy energy without NSAID pretreatment (n = 20 eyes); FLACS with 90% capsulotomy energy with NSAID pre-treatment (n = 21 eyes); and FLACS with 150% capsulotomy energy with NSAID pretreatment (n = 22 eyes). Aqueous humor was collected before and after phacoemulsification to assess cytokine profiles. Pupil size was measured before and after laser capsulotomy. RESULTS: FLACS increased aqueous concentrations of pros-taglandin E2 (PGE2), interferon γ (IFN-γ), and interleukin 6 (IL-6) compared to conventional phacoemulsification. However, when increasing capsulotomy energy from 90% to 150% (with topical NSAID pretreatment), there was no significant increase in aqueous concentrations of PGE2 (37.7 ± 21.7 vs 33.6 ± 27.6 pg/mL, P = .99), IFN-γ (3.6 ± 1.1 vs 3.6 ± 0.8 pg/mL, P = .99), or IL-6 (7.1 ± 2.9 vs 6.3 ± 2.4 pg/mL, P = .99). For 90% and 150% capsulotomy energy, there was significant miosis following laser capsulotomy. Increased PGE2 concentration was significantly correlated with a reduction in pupil area (r = -0.58, P < .001) and pupil diameter (r = -0.57, P < .001). However, when a topical NSAID was given preoperatively, there was no difference in the degree of miosis between the 90% and 150% capsulotomy energy groups. CONCLUSIONS: Pretreatment with a topical NSAID prevented a rise in PGE2, IFN-γ, and IL-6 levels and excessive miosis when a higher capsulotomy energy was used. When a topical NSAID is used preoperatively, it is safe to use higher capsulotomy energy settings (with a low pulse energy femtosecond laser system) to achieve a satisfactory capsulotomy. [J Refract Surg. 2022;38(9):587-594.].

Case Report: Peripheral Ulcerative Keratitis in Systemic Solid Tumour Malignancies.

Purpose: To describe a case series of peripheral ulcerative keratitis (PUK) as a paraneoplastic condition in three patients with known underlying systemic solid tumor malignancies. Observations: Three patients with different systemic malignancies (1 recurrent breast cancer, 1 metastatic thyroid cancer, and 1 metastatic gastric adenocarcinoma) were identified to have PUK with significant corneal stromal melt. Autoimmune and infective work up for other etiologies were all negative. They all responded well to topical steroids and intravenous methylprednisolone. One patient had recurrences of her PUK and required repeated amniotic grafts and tectonic keratoplasties before her corneal condition stabilized. Conclusions and Importance: PUK can be a rare manifestation of systemic solid tumor malignancies. Although PUK may not be an indicator of progression of the underlying malignancy, it can be sight-threatening. This case series highlights the necessity for clinicians to refer patients with systemic malignancies presenting with inflamed eyes for an early ophthalmological review. This facilitates the detection of this blinding disease, allowing for early therapeutic interventions and potentially better visual outcomes for these patients.

Drug induced cicatrizing conjunctivitis: A case series with review of etiopathogenesis, diagnosis and management.

Drug induced cicatrizing conjunctivitis (DICC) is defined as a disease in which conjunctival cicatrization develops as a response to the chronic use of inciting topical and, rarely, systemic medications. DICC accounts for up to one third of cases of pseudopemphigoid, a large group of cicatrizing conjunctival diseases sharing similar clinical features to those of mucous membrane pemphigoid (MMP) but generally without the morbidity of progressive scarring or the need for systemic immunosuppression. The preservatives in topical anti-glaucoma medications (AGM) are the most frequently implicated inciting causes of DICC although topical antivirals, vasoconstrictors and mydriatics and some systemic drugs have been implicated. The literature review summarizes the classification, epidemiology, etiopathogenesis, histopathology, clinical presentation, diagnosis, management, and treatment outcomes of DICC in the context of a case series of 23 patients (42 eyes) with AGM induced DICC, from India and the UK. In this series all subjects reacted to preserved AGM with one exception, who also reacted to non-preserved AGM. At diagnosis >70% of eyes showed punctal scarring, inflammation, and forniceal shortening. Pemphigoid studies were negative in the 19/23 patients in whom they were carried out. DICC can be classified as non-progressive, progressive with positive pemphigoid immunopathology or progressive with negative pemphigoid immunopathology. It is unclear whether progressive DICC is a stand-alone disease, or concurrent (or drug induced) ocular MMP. Progressive cases should currently be treated as ocular MMP. The diagnosis can be made clinically when there is rapid resolution of symptoms and inflammation, usually within 1-16 weeks, after withdrawal of suspected inciting medications, ideally by temporary substitution of oral carbonic anhydrase inhibitors. If the response to withdrawal is uncertain, or the progression of inflammation and scarring continues then patients must be evaluated to exclude concurrent (or drug induced) MMP, and other potential causes of CC, for which the treatment and prognosis is different. Management, in addition to withdrawing inciting medications, may require short-term treatment of conjunctival inflammation with steroids, treatment of associated corneal disease with contact lenses or surface reconstructive surgery, control of intra-ocular pressure with non-preserved AGM and, in some, surgery for glaucoma or for trichiasis and entropion.

Centration and Stability of Small-Aperture Intraocular Lens in Aberrated Eyes.

PURPOSE: To investigate the visual outcomes and postoperative stability of IC-8 intraocular lens (AcuFocus, Inc) implantation following femtosecond laser-assisted cataract surgery. METHODS: In this prospective study, the IC-8 IOL was implanted in the non-dominant eye of 12 patients. Centration and uncorrected and corrected distance, intermediate, and near visual acuities (UDVA, UIVA, UNVA, CDVA, CIVA, CNVA) were evaluated up to postoperative month 3 (POM3). Means ± standard deviations are reported in logMAR units. RESULTS: There were no significant differences in absolute, vertical, and horizontal centration postoperatively versus intraoperatively. From intraoperative to POM3, mean displacement was 0.17 ± 0.09 and 0.14 ± 0.07 mm (P = .52) relative to the capsulorhexis and 0.28 ± 0.22 and 0.25 ± 0.14 mm relative to the limbus (P = .62), respectively. Centration remained within the 1.36-mm IC-8 aperture. Excluding patients with ocular comorbidities, from preoperatively to POM3, UDVA improved significantly from 0.52 ± 0.39 to 0.20 ± 0.11 logMAR (P = .024), with an efficacy index of 0.80 ± 0.31. The safety index was 1.30 ± 0.40, with no adverse events experienced. At POM3, CDVA, UIVA, and UNVA of 0.04 ± 0.05, 0.27 ± 0.11, and 0.22 ± 0.10 logMAR were achieved, respectively. Binocularly, all achieved UDVA of 20/25 or better and UIVA and UNVA of N6 and better. CONCLUSIONS: The IC-8 IOL can attain good centration and positional stability up to POM3. It enables both extended depth of focus and tolerance to aberration, making it capable of achieving spectacle independence after surgery. [J Refract Surg. 2022;38(2):98-105.].

The effects of laser displacement on femtosecond laser-assisted conjunctival autograft preparation for pterygium surgery.

AIMS: To evaluate the effects of no-suction femtosecond laser (FSL) stability on conjunctival autograft (CAG) dissection in pterygium surgery. METHODS: Prospective analysis of 35 eyes from 34 subjects who underwent femtosecond laser-assisted pterygium surgery with the Ziemer Z8 laser (Ophthalmic Systems AG, Switzerland). Intraoperative absolute FSL displacements were measured and correlated with the duration and ease of CAG peel, CAG thickness, measured with intraoperative optical coherence tomography, and deviation from intended graft thickness. RESULTS: The median absolute FSL displacement was 22 µm (interquartile range [IQR] 14.7 to 60.8), while median vertical FSL displacement was 14.7 µm (IQR 7.3 to 44) and median horizontal FSL displacement was 22.0 µm (IQR 14.7 to 44). 65.7% had a grade 1 peel, 11.4% had grade 2 peel, 14.3% had grade 3 peel and 8.6% had grade 4 peel. The median duration of CAG peel was 5.4 seconds (IQR 3 to 21.4). The median CAG thickness was 69 µm (IQR 60.3 to 78.5), and the median deviation from targeted graft thickness was 9 µm (IQR 1 to 16). Eyes with more difficult peels and longer duration of CAG peels had significantly greater vertical FSL displacements (p = 0.04 and 0.02 respectively), but not horizontal displacement, age, ethnicity, CAG thickness or deviation from original thickness, compared to those with better quality and shorter duration peels. 1 eye (2.9%) had an incomplete CAG peel with a buttonhole and 2 eyes had graft tears (5.7%). CONCLUSION: Micro-displacements during the suction-free CAG preparation are common but they did not affect the quality of the CAG peel, duration of peel, or CAG thickness. However, vertical globe displacement during FSL-assisted CAG creation was significantly associated with a more difficult and longer CAG peel duration. This highlights the importance of the cornea traction suture fixation to ensure stability of the eye during FSL application.

Randomized Controlled Trial Comparing 1-Year Outcomes of Low-Energy Femtosecond Laser-Assisted Cataract Surgery versus Conventional Phacoemulsification.

Purpose: To compare 1-year clinical outcomes, phacoemulsification energy, aqueous profiles, and patient-reported outcomes of low-energy femtosecond laser-assisted cataract surgery (FLACS) vs. conventional phacoemulsification. Methods: The study is a randomized controlled trial (RCT) with paired-eye design. Eighty-five patients were randomized to receive FLACS (Ziemer LDV Z8) in one eye and conventional phacoemulsification in the fellow eye. Clinical data including phacoemulsification energy parameters (cumulative dissipated energy, phacoemulsification power, and phacoemulsification time), uncorrected and corrected distance visual acuities (UCDVA and BCDVA), manifest refraction spherical equivalent (MRSE), central corneal thickness (CCT), endothelial cell count (ECC), anterior chamber flare, and post-operative complications were obtained for 1 year. Aqueous humor was collected for the analysis of prostaglandin (PGE)2, cytokines and chemokines concentrations. Patients' reported-outcomes on surgical experiences were evaluated using an in-house questionnaire. Results: Compared to conventional phacoemulsification, the low-energy assisted FLACS group had significantly less ECC reduction at 3 months (1.5 ± 0.3% vs. 7.0 ± 2.4%; P < 0.01) and 1 year (8.2 ± 2.8% vs. 11.2 ± 3.6%; P = 0.03). There were no significant differences in the phacoemulsification energy parameters, UCDVA, BCDVA, MRSE, CCT, occurrence of post-operative complications between the 2 groups throughout post-operative 1 year. Patients' subjective surgical experiences, including the surgical duration and perceived inconvenience, were comparable between the 2 groups. FLACS resulted in significantly higher aqueous PGE2 (P < 0.01), interleukin (IL)-6 (P = 0.03), IL-8 (P = 0.03), and interferon (IFN)-γ (P = 0.04) concentrations and greater anterior chamber flare at 1 day (P = 0.02). Conclusions: Our RCT presented 1-year longitudinal clinical and laboratory data. The long-term ECC result was more favorable in low-energy FLACS. The rest of the intraoperative and post-operative outcomes, as well as patient-reported outcomes, were comparable between these two procedures.

Evolution of therapies for the corneal endothelium: past, present and future approaches.

Corneal endothelial diseases are leading indications for corneal transplantations. With significant advancement in medical science and surgical techniques, corneal transplant surgeries are now increasingly effective at restoring vision in patients with corneal diseases. In the last 15 years, the introduction of endothelial keratoplasty (EK) procedures, where diseased corneal endothelium (CE) are selectively replaced, has significantly transformed the field of corneal transplantation. Compared to traditional penetrating keratoplasty, EK procedures, namely Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK), offer faster visual recovery, lower immunological rejection rates, and improved graft survival. Although these modern techniques can achieve high success, there are fundamental impediments to conventional transplantations. A lack of suitable donor corneas worldwide restricts the number of transplants that can be performed. Other barriers include the need for specialized expertise, high cost, and risks of graft rejection or failure. Research is underway to develop alternative treatments for corneal endothelial diseases, which are less dependent on the availability of allogeneic tissues - regenerative medicine and cell-based therapies. In this review, an overview of past and present transplantation procedures used to treat corneal endothelial diseases are described. Potential novel therapies that may be translated into clinical practice will also be presented.

Meibomian gland dysfunction is the primary determinant of dry eye symptoms: Analysis of 2346 patients.

PURPOSE: To determine relative contributions of various ocular surface clinical signs and predisposing factors to the magnitude of dry eye symptoms. METHODS: Clinical audit data were prospectively collected for newly referred dry eye patients. All 2346 patients had an initial visit evaluation of the Ocular Surface Disease Index (OSDI), and a detailed ophthalmic examination including tear breakup time (TBUT), ocular surface fluorescein staining, Schirmer's I test. Among the participants, 1414 had number of liquid meibum expressing glands (NLMEG) evaluated on standard force expression. Other variables collected included history of glaucoma or glaucoma surgery, and history of allergies. RESULTS: In patients aged 46.2 ± 14.8 years, 77.4% were women and 87.1% Chinese. The mean ± SD OSDI was 35.2 ± 21.7. On univariate analysis, higher OSDI was associated with glaucoma diagnosis (p = 0.003), glaucoma surgery (p = 0.002), greater temporal corneal staining (p = 0.002), reduced NLMEG (p < 0.001), and higher inferior forniceal papillary grade (p < 0.001). OSDI was not significantly associated with gender, TBUT, Schirmer's I test values, or the use of cyclosporine eyedrops. On multivariate regression, higher OSDI scores were associated with fewer NLMEG (p = 0.002) and increased lower eyelid forniceal papillary grading (p = 0.002). Corneal staining, glaucoma status and glaucoma surgery were not significantly associated with OSDI. Logistic regression showed that severe symptoms (OSDI>32) was associated with <2 NLMEG [OR(95%CI): 1.34(1.08-1.66)], and presence of inferior eyelid forniceal papillae [1.50(1.17-1.91)]. CONCLUSIONS: Meibomian gland dysfunction (MGD) and lower forniceal papillary reaction had significant contributions to the severity of symptoms, in contrast to traditional dry eye signs. MGD should be objectively assessed and treated to improve symptoms.

Corneal Ectasia Risk And Percentage Tissue Altered In Myopic Patients Presenting For Refractive Surgery.

PURPOSE: A percentage tissue altered (PTA) score of ≥40% has been advocated as an independent indicator of post-operative ectasia risk following laser in-situ keratomileusis (LASIK). This study was performed to test the hypothesis that refractive procedures, such as laser-assisted sub-epithelial keratectomy (LASEK) or small incision lenticule extraction (SMILE), may alter the range of PTA, within which refractive corneal surgery can be safely performed. SETTING: Refractive department, tertiary ophthalmic hospital. DESIGN: Retrospective observational study. METHODS: Review of case notes was performed for patients who presented for refractive surgeries, other than LASIK. To determine the risk of corneal ectasia for each patient prior to refractive surgery, we estimated what each patient's PTA would have been if they had undergone LASIK. The Randleman Ectasia Risk Score System (ERSS) was also calculated. RESULTS: 114 eyes (66 patients) were included. 94 eyes underwent SMILE. 20 eyes underwent LASEK. A significant proportion of eyes had PTA ≥40% - SMILE eyes: up to 31.9%, LASEK eyes: up to 60.0% (at presumed LASIK flap of 120 µm). The maximum calculated PTA was up to 47.9% in the SMILE group and up to 51.5% in the LASEK group. Using ERSS, 12.8-16% of SMILE eyes and 15.0-80.0% of LASEK eyes would have been considered to have moderate-to-high ectasia risk. No post-surgical ectasia was observed at 3 years. CONCLUSION: SMILE and LASEK alter the range of PTA, within which corneal refractive surgery may be performed with a lower risk of developing post-operative corneal ectasia; a safe PTA threshold needs to be determined for these procedures before recommendations for clinical practice can be made.

Optical Coherence Tomography Angiography Imaging to monitor Anti-VEGF treatment of Corneal Vascularization in a Rabbit Model.

Optical coherence tomography angiography (OCTA) is a well-established non-invasive retinal vascular imaging technique. It has been recently adapted to image the anterior segment and has shown good potential to image corneal vascularisation. The purpose of the study is to evaluate the usefulness of OCTA to monitor regression of corneal vessels following anti-VEGF (vascular endothelial growth factor) treatment using a previously established corneal vascularisation rabbit model. The regression of vessels following the treatment with aflibercept and ranibizumab anti-VEGFs using both topical instillation and sub-conjunctival injection was quantified using OCTA and compared with ICGA (indocyanine green angiography). Overall vessel density measurements using OCTA showed good correlation (r = 0.988, p < 0.001) with ICGA, with no significant difference between the two treatment groups (p = 0.795). It was also shown that OCTA provided good repeatability outcomes of the quantitative measurements. Using Bland-Altman plots, vessel growth density values between anti-VEGF treatments were compared to control saline group. It was observed that aflibercept provided longer lasting effect than ranibizumab. We also observed that in both drugs, the topical route of administration topical provided longer regression outcomes compared to one-time sub-conjunctival injection. Thereby, with this pilot study, it was demonstrated that OCTA is a reliable imaging technique to follow-up and monitor corneal vascularisation and its treatment quantitatively.

Current Trends and Future Perspective of Mesenchymal Stem Cells and Exosomes in Corneal Diseases.

The corneal functions (transparency, refractivity and mechanical strength) deteriorate in many corneal diseases but can be restored after corneal transplantation (penetrating and lamellar keratoplasties). However, the global shortage of transplantable donor corneas remains significant and patients are subject to life-long risk of immune response and graft rejection. Various studies have shown the differentiation of multipotent mesenchymal stem cells (MSCs) into various corneal cell types. With the unique properties of immunomodulation, anti-angiogenesis and anti-inflammation, they offer the advantages in corneal reconstruction. These effects are widely mediated by MSC differentiation and paracrine signaling via exosomes. Besides the cell-free nature of exosomes in circumventing the problems of cell-fate control and tumorigenesis, the vesicle content can be genetically modified for optimal therapeutic affinity. The pharmacology and toxicology, xeno-free processing with sustained delivery, scale-up production in compliant to Good Manufacturing Practice regulations, and cost-effectiveness are the current foci of research. Routes of administration via injection, topical and/or engineered bioscaffolds are also explored for its applicability in treating corneal diseases.

Urea-De-Epithelialized Human Amniotic Membrane for Ocular Surface Reconstruction.

The conjunctiva is a clear tissue covering the white part of the eye and lines the back of the eyelids. Conjunctival diseases, such as symblepharon, cause inflammation, discharges, and photophobia. The treatment often requires excision of large parts of conjunctiva. Tissue engineering of conjunctival cells using human amniotic membrane (HAM) denuded of its epithelium as a basement membrane scaffold has been shown to be effective for covering conjunctival defects. However, most epithelial denudation protocols are time-consuming and expensive or compromise HAM's basement membrane structure and matrix components. We have previously described a method to de-epithelialize HAM using ice-cold urea (uHAM). In this report, we used this method to provide tissue-engineered constructs with cultivated conjunctival epithelial cells on uHAM in two patients, one with a giant conjunctival nevus and the other with a large symblepharon. Autologous conjunctival epithelial cells harvested from incisional biopsies of these two patients were cultured on the uHAM scaffold. The transplantation of tissue-engineered constructs to patients' ocular surface immediately after the removal of lesions showed successful reconstruction of the ocular surface. Postoperatively, there were neither recurrence of lesions nor epithelial defects throughout the follow-up (up to 7 and 19 months, respectively). This report highlights the translational potential of an efficient and inexpensive method to prepare de-epithelialized HAM as a basement membrane scaffold for cell-based tissue-engineered treatments of ocular surface disorders. Stem Cells Translational Medicine 2019;8:620&626.

Corneal Inlays for Presbyopia Explanted Due to Corneal Haze.

PURPOSE: To present 3 patients who required explantation of KAMRA inlays (AcuFocus, Inc., Irvine, CA) due to visual symptoms caused by postoperative corneal haze. METHODS: Case series. RESULTS: All patients had good near and distance vision immediately following implantation. They developed visual symptoms 3 to 6 years later. All patients reported a decline in distance vision. Two patients had hyperopic shift with flattening of the central cornea. Six months following explantation, all patients reported improvement in visual symptoms. A reversal of hyperopic shift was also observed, with improvement in corneal profiles on topography. Histopathology of the explanted inlays showed thin, acellular collagenous fibrotic membranes over the inlays with occasional chronic inflammatory cells. CONCLUSIONS: It is important for health care professionals to be made aware of this reversible complication following KAMRA inlay implantation. Long-term monitoring is recommended. [J Refract Surg. 2018;34(5):357-360.].

Mucous Membrane Pemphigoid with Ocular Involvement: The Clinical Phenotype and Its Relationship to Direct Immunofluorescence Findings.

PURPOSE: This study explored the validity of the First International Consensus on Mucous Membrane Pemphigoid (MMP) guidance, which recommends that clinically indistinguishable patients, who have direct immunofluorescence (DIF)-negative biopsies, be excluded from a diagnosis of MMP. Misdiagnosis, or delayed diagnosis, of MMP with ocular involvement leads to the inappropriate use of topical therapy, the standard of care for causes of cicatrising conjunctivitis other than MMP, rather than systemic immunomodulatory therapy, resulting in irreversible clinical deterioration in patients with MMP. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Patients meeting the clinical criteria of ocular MMP, including those with positive and negative DIF findings. METHODS: A case report form was used to collect the demographic details, the clinical history, and the results of a detailed clinical assessment by ophthalmologists, otolaryngologists, dermatologists, and oral medicine specialists. All anatomic sites potentially affected by MMP were examined apart from the esophagus (and larynx in a subset). The DIF results were recorded. MAIN OUTCOME MEASURES: Differences between DIF-positive and -negative patients in demography, sites of involvement, and disease severity as determined by the degree of conjunctival scarring (using Tauber staging), central corneal disease (vascularization, scarring, ulceration, and conjunctivalization), history of conjunctival or lid surgery, and requirement for systemic immunotherapy at the time of screening. RESULTS: A total of 73 patients with ocular MMP were recruited, of whom 20 of 73 (27.4%) had ocular-only disease. There was no significant demographic or clinical difference between patients with positive and negative DIF results. This finding included differences in disease severity for which the only significant difference was that of more severe central corneal disease in DIF-negative patients. Asymptomatic disease at different sites was frequent. CONCLUSIONS: These findings do not support the classification of DIF-negative patients, meeting the clinical criteria for ocular MMP, as having a different disease. This category of patients should be accepted as having DIF-negative MMP, for clinical management purposes, with patients having inflamed eyes being treated with systemic immunomodulatory therapy. The frequent finding of asymptomatic ocular, oral, and nasopharyngeal MMP is clinically significant and implies that these sites should be routinely screened in asymptomatic patients.