Search

Aim: To evaluate whether the Visian Implantable Collamer Lens with a central port (V4c ICL®; STAAR Surgical, Switzerland) affects the retinal nerve fibre layer (RNFL), macula and optic nerve head (ONH) measurements obtained by optical coherence tomography (OCT), and Heidelberg Retina Tomography (HRT)., Methods: This prospective study included myopic patients undergoing V4c ICL® implantation. RNFL thickness, macular thickness, ganglion cell analysis (GCA) and ONH main parameters were evaluated with RTVue OCT (Optovue Inc., USA) and Cirrus-HD OCT (Carl Zeiss Meditec, USA). ONH variables were also analysed with HRT-3 (Heidelberg Engineering, Germany). All measurements were performed before and 1 week and 12 months after the surgery., Results: 31 eyes of 31 patients (mean age 30.1 ± 5.5 years) were included. Comparing with preoperative values, no significant differences in average RNFL thickness were found with RTVue, while a slight increase (4.3 µm) was detected with Cirrus-HD (85.2 ± 10.3 µm, preoperatively) at 1-week postoperatively (89.5 ± 8.3 µm; p < 0.05). Those changes were not observed at the last follow-up visit (86.6 ± 8.6 µm; p = 0.41). Cirrus-HD detected that macular thickness was slightly higher 1 week after surgery, compared with the preoperative examination (3.4% increase; p = 0.04). That difference remained stable at the 12-month postoperative visit (p = 0.01). GCA showed no changes. The ONH analysis with Cirrus-HD determined that rim area (p = 0.03) as well as disc area (p = 0.04) significantly increased. HRT-3 found no significant changes affecting those variables., Conclusions: The implantation of V4c ICL® did not induce a clinically significant impact on the results of the RNFL/ONH analysis with OCT and HRT.

The cornea is a densely innervated avascular tissue showing exceptional inflammatory and immune responses. The cornea is a site of lymphangiogenic and angiogenic privilege devoid of blood and lymphatic vessels that limits the entry of inflammatory cells from the adjacent and highly immunoreactive conjunctiva. Immunological and anatomical differences between the central and peripheral cornea are also necessary to sustain passive immune privilege. The lower density of antigen-presenting cells in the central cornea and the 5:1 peripheral-to-central corneal ratio of C1 are two main features conferring passive immune privilege. C1 activates the complement system by antigen-antibody complexes more effectively in the peripheral cornea and, thus, protects the central corneas' transparency from immune-driven and inflammatory reactions. Wessely rings, also known as corneal immune rings, are noninfectious ring-shaped stromal infiltrates usually formed in the peripheral cornea. They result from a hypersensitivity reaction to foreign antigens, including those of microorganism origin. Thus, they are thought to be composed of inflammatory cells and antigen-antibody complexes. Corneal immune rings have been associated with various infectious and noninfectious causes, including foreign bodies, contact lens wear, refractive procedures, and drugs. We describe the anatomical and immunologic basis underlying Wessely ring formation, its causes, clinical presentation, and management., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Many factors in the domains of mental, physical, and social health have been associated with various ocular surface diseases, with most of the focus centered on aspects of dry eye disease (DED). Regarding mental health factors, several cross-sectional studies have noted associations between depression and anxiety, and medications used to treat these disorders, and DED symptoms. Sleep disorders (both involving quality and quantity of sleep) have also been associated with DED symptoms. Under the domain of physical health, several factors have been linked to meibomian gland abnormalities, including obesity and face mask wear. Cross-sectional studies have also linked chronic pain conditions, specifically migraine, chronic pain syndrome and fibromyalgia, to DED, principally focusing on DED symptoms. A systematic review and meta-analysis reviewed available data and concluded that various chronic pain conditions increased the risk of DED (variably defined), with odds ratios ranging from 1.60 to 2.16. However, heterogeneity was noted, highlighting the need for additional studies examining the impact of chronic pain on DED signs and subtype (evaporative versus aqueous deficient). With respect to societal factors, tobacco use has been most closely linked to tear instability, cocaine to decreased corneal sensitivity, and alcohol to tear film disturbances and DED symptoms., Competing Interests: Declaration of competing interest Anat Galor: Novartis (C), Novaliq (C), Oyster Point Pharma (C), Palatin Technologies (C), Oculis (C), Dompé (C), Allergan (C), Shire (C) Alexis Ceecee Britten-Jones: Plano (R) Yun Feng: None. Giulio Ferrari: Bausch + Lomb (F) David Goldblum: Roche (F), Novartis (P), Haag-Streit (C), Johnson & Johnson Vision (C) Preeya K. Gupta: Alcon (C), Allergan (C), Aldeyra (C), Azura (C), Expert Opinion (C), HanAll Biopharma (C), Johnson & Johnson Vision (C), Kala (C), New World Medical (C), Novartis (C), Ocular Science (C), Ocular Therapeutix (C), Orasis (C), Oyster Point Pharma (C), Santen (C), Spyglass (C), , Sight Sciences (C), Surface Ophthalmics (C), Sun Pharmaceuticals (C), Tarsus (C), Tear Lab (C), Tear Clear (C), Tissue Tech (C), Visionology (C), Zeiss (C) Jesus Merayo-Lloves: BTI + d(C), Brill(C), Faes Pharma, Sophia(C), Théa (C) Kyung-Sun Na: None. Shehzad A. Naroo: None. Kelly K. Nichols: Azura (F), Tear Science (F), Oyster Point Pharma (I,C), Bausch + Lomb (C), Bruder (C), Dompé (C), HanAll Bio (C), Kala (F,C), Novartis/Shire/Takeda (C), Osmotica (F), Sight Sciences (F), Tear Film Innovations/Alcon/Acquiom (C), Thea (C), Tarsus (C), TopiVert (C), Trukera (C), Versea (C), Xequel (C), Nicox (C), Novaliq (C) Eduardo M. Rocha: Christalia Lab ( Louis Tong: Azura (C), Allergan (C), Santen (C), Alcon/Novartis (F,R), Bausch + Lomb (R), Vivavision Biotech (C) Michael T. M. Wang: None. Jennifer P. Craig: Adelphi Values Ltd (R), Alcon (F,R,C), Asta Supreme (R), Azura Ophthalmics (F,R), E-Swin (F,R), Johnson & Johnson Vision (R), Manuka Health (F), Medmont International (R), Novoxel (R), Oculeve (F), Photon Therapeutics (R), Resono Ophthalmic (F,R), TFOS (S), Th'ea Laboratories (F,R), Topcon (F,R), TRG Natural Pharmaceuticals (F,R)., (Published by Elsevier Inc.)

Aim: To investigate the difference in adhesion and rebubbling rate between eye bank and surgeon prepared Descemet membrane endothelial keratoplasty (DMEK) tissues., Methods: Laboratory and clinical retrospective comparative interventional case series. Research corneal tissues were obtained for laboratory investigation. The clinical study involved patients with endothelial dysfunction who underwent DMEK surgery and tamponade with air. Tissues were stripped using a standard DMEK stripping technique (SCUBA) and shipped as prestripped or loaded in a 2.2 intra-ocular lens cartridge with endothelium facing inwards (preloaded) before transporting from the eye bank to the surgeon. For surgeon prepared tissues, all the grafts were stripped in the theatre and transplanted or stripped in the laboratory and tested immediately. Adhesion force and elastic modulus were measured in the centre and mid-periphery in a laboratory ex vivo investigation using atomic force microscopy, while rebubbling rates were recorded in the clinical study., Results: There was no difference in endothelial cell viability between surgeon or eye bank prepared tissue. Surgeon-stripped DMEK grafts in the laboratory investigation showed significantly higher elastic modulus and adhesion force compared to prestripped and preloaded tissues (p<0.0001). In the clinical data, rebubbling rates of 48%, 40% and 15% were observed in preloaded, prestripped and surgeon-stripped DMEK grafts, respectively. Rebubbling rates were significantly associated with combined cataract surgery (p=0.009) and with time from harvesting the graft to the surgery (p=0.02)., Conclusions: Decreased adhesion forces and elastic modulus in eye bank prepared tissues may contribute to increased rebubbling rates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

The ocular surface flora perform an important role in the defense mechanisms of the ocular surface system. Its regulation of the immunological activity and the barrier effect against pathogen invasion are remarkable. Composition of the flora differs according to the methods of investigation, because the microbiome, composed of the genetic material of bacteria, fungi, viruses, protozoa, and eukaryotes on the ocular surface, differs from the microbiota, which are the community of microorganisms that colonize the ocular surface. The observed composition of the ocular surface flora depends on harvesting and examining methods, whether with traditional culture or with more refined genetic analysis based on rRNA and DNA sequencing. Environment, diet, sex, and age influence the microbial flora composition, thus complicating the analysis of the baseline status. Moreover, potentially pathogenic organisms can affect its composition, as do various disorders, including chronic inflammation, and therapies applied to the ocular surface. A better understanding of the composition and function of microbial communities at the ocular surface could bring new insights and clarify the epidemiology and pathology of ocular surface dynamics in health and disease. The purpose of this review is to provide an up-to-date overview of knowledge about this topic., (Copyright © 2021. Published by Elsevier Inc.)

Abstract: To evaluate the efficacy and safety of plasma rich in growth factors (PRGF) in photorefractive keratectomy (PRK) versus Mitomycin C (MMC).This is a comparative, longitudinal and retrospective case-control study (MMC vs PRGF), in patients with a spherical correction from -0.25 to -8.00 D and cylinder correction from -0.25 to -3.00. The uncorrected distance visual acuity (UDVA), refractive efficacy and safety indices, and changes in endothelial cell density were evaluated. The predictability was assessed with the postoperative manifest spherical equivalent.Forty-four patients (72 eyes) were treated with MMC and twenty-five patients (45 eyes) with PRGF. The final UDVA (LogMar) in MMC was 0.029 ± 0.065 and in PRGF it was 0.028 ± 0.048 (p = 0.383). The efficacy index for MMC was 0.98 ± 0.10 and 1.10 ± 0.46 for patients treated with PRGF (p = 0.062). The safety index for MMC was 1.03 ± 0.11 and 1.12 ± 0.46 (p = 0.158) for PRGF group. The change percentage of endothelial cell density was 0.9 ± 11.6 for MMC and 4.3 ± 13.1 for PRGF (p = 0.593). The predictability for MMC was 92.1% and for the PRGF was 91.9% (p = 0.976). Hyperemia, eye pain and superficial keratitis were observed in 11.1% of the MMC group; no adverse events were observed with the PRGF.The use of PRGF in PRK surgery is as effective as MMC. The PRGF shows a better safety profile than MMC for its intraoperative use in PRK., Competing Interests: The authors declare the following competing financial interest(s): E.A. is the Scientific Director of BTI Biotechnology Institute, R.M.S.A and F.M are scientists at BTI Biotechnology Institute, a dental implant company, that investigates in the fields of oral implantology and PRGF-Endoret technology. The rest of the authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Neurotrophic keratopathy (NK) is a degenerative corneal disease produced by different factors, including infection, trauma, and neurogenesis, that lead to trigeminal nerve damage and impaired corneal sensitivity. Extensive epithelial breakdown, impaired corneal epithelial healing and corneal ulceration, stromal melting, and perforation are main NK features. The proliferation of the corneal epithelium is endogenously regulated by a balance between adrenergic cAMP-dependent and cholinergic cGMP-dependent pathways. A careful balance of epitheliotropic neuromediators and neurotrophic factors expressed by corneal nerves and epithelial cells, respectively, is required to maintain corneal homeostasis. Even in its early stages, NK can cause reduced vision secondary to epithelial disturbance. Diagnosing NK is challenging, requiring the acquisition of a thorough clinical history and a comprehensive neurological and ophthalmic examination. Following suspicion of a clinical NK diagnosis, corneal sensitivity must be assessed qualitatively with the wisp of the cotton-tipped applicator and quantitatively through Cochet-Bonnet esthesiometry (CBE). A myriad of therapies is used for NK, and new, more specific modalities are being developed and investigated. Medical treatment with topical recombinant human nerve growth factor and surgical treatment through corneal neurotization are promising therapies aiming to target NK pathophysiology. Coexistent ocular surface disorders must be managed concomitantly to improve its prognosis. This review describes the up-to-date knowledge of the molecular basis regarding the pathogenesis of NK, and the novel target-specific therapeutic approaches based on this molecular mechanism., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: This study analysed the effectiveness of plasma rich in growth factors (PRGF) in reducing the oxidative stress induced by blue light exposition on retinal pigment epithelial (RPE) cells., Methods: Blood from six healthy donors was collected to obtain the PRGF. Retinal pigment epithelium (ARPE-19) cells were exposed to blue light. Then, cells were incubated with PRGF or with control for 24 and 48 hours maintaining exposure to blue light. The cytoprotective effect of PRGF on ARPE cells was evaluated by measuring the cell viability, the reactive oxygen species (ROS) production and the expression of different proteins such as heme oxygenase 1 (HO-1), catalase (CAT), superoxide dismutase (SOD-1), apoptosis-inducing factor (AIF), pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF)., Results: The cell viability increased significantly at 24 and 48 hours after PRGF treatment compared to the control group. ROS synthesis was significantly reduced in PRGF-treated cells with respect to control. Furthermore, the levels of HO-1, SOD-1 and AIF were significantly reduced after PRGF treatment at both times of treatment. However, CAT levels were only significantly reduced after PRGF treatment at 48 hours. The high expression of VEGF by RPE cells exposed to blue light was only counterbalanced in the PRGF group by increasing the expression of PEDF in comparison to the control group., Conclusion: The present results show that PRGF treatment reduces the cytotoxic effects induced in RPE cells exposed to an oxidative stress environment. Furthermore, PRGF treatment preserves the mitochondrial activity and cell viability of RPE cells subjected to an oxidative stress., (© 2020 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: To evaluate the efficacy and safety of plasma rich in growth factors eye drops for the treatment of corneal and ocular surface disorders in patients with graft versus host disease., Methods: This retrospective and longitudinal study included graft versus host disease patients with ocular disorders. The resolution of corneal ulcers (area and density staining) was evaluated as primary outcome. Best corrected visual acuity, intraocular pressure, tear film breakup time, Schirmer test, ocular surface disease index, and visual analog score were evaluated as secondary outcomes. All variables were analyzed before and after plasma rich in growth factors treatment. The safety of plasma rich in growth factors treatment was also assessed., Results: Twelve patients (23 eyes) with ocular graft versus host disease were evaluated. Statistically significant improvement in the area (75.7%) and density (73.3%) of the corneal staining, in best corrected visual acuity (74.7%), in ocular surface disease index scale (75.4%), visual analog score frequency (81.4%) and visual analog score severity (81.9%), and an increase of 3.8 s in tear film breakup time and 6 mm in Schirmer test was observed after plasma rich in growth factors treatment (p < 0.001). Some potential modifiers of the therapeutic effect were identified. All patients achieved corneal stability without perforation risk. No adverse events associated with the plasma rich in growth factors were observed., Conclusion: Immunosafe plasma rich in growth factors eye drops for the treatment of patients with ocular graft versus host disease could be safe and effective, showing a high rate of corneal ulcer resolution and dry eye disease control. Plasma rich in growth factors eye drops may help to maintain corneal stability and prevent it against higher ocular complications.

Purpose: To provide preliminary data about efficacy and safety of plasma rich in growth factors (PRGF) eye-drops in neurotrophic keratitis (NK) and to analyze the possible influence of certain variables on treatment outcomes., Methods: This retrospective study included patients with stages 2-3 of NK treated with PRGF eye-drops. Primary endpoint was the resolution time of corneal ulcer defect. Outcome measures including percentage of ulcer closure at 4 weeks, Ocular Surface Disease Index (OSDI), Best-Corrected Visual Acuity (BCVA) and Visual Analogue Scale (VAS) were also evaluated before and after treatment with PRGF. The influence of some patients' clinical variables on results was assessed. Safety assessment was also performed reporting all adverse events., Results: Thirty-eight treated eyes in a total of thirty-one patients were evaluated, of which five cases had no prior response to autologous serum treatment. Most cases (97.4%) achieved the complete resolution of corneal defect/ulcer. Mean resolution time was 11.4 weeks (SD = 13.7). A statistical significant (p < 0.05) reduction in OSDI (60.9%), VAS frequency (59.9%), VAS severity (57.0%) and improvement in BCVA (52.8%) was observed. The results were stratified according to the pathology stage and to the identified potential effect modifiers variables. Only one adverse event was reported in one patient (2.6%)., Conclusions: PRGF eye-drops could be a safe and effective therapeutic option for patients with stages 2-3 of NK, showing high rates of corneal defect/ulcer resolution in short times, either in reducing signs and symptoms of NK, and therefore preventing the progression of NK to greater ocular complications.

Purpose: To evaluate the efficacy and safety of plasma rich in growth factors (PRGF) eye drops in patients with glaucoma with secondary ocular surface disorders (OSDs) due to surgeries and topical hypotensive drugs use., Materials and Methods: A retrospective case-series study design was used including six patients (eight eyes) diagnosed with glaucoma who received surgical (nonpenetrating deep sclerectomy and/or trabeculectomy) and medical treatments (hypotensive eye drops) to control intraocular pressure (IOP) and who developed secondary OSDs, unresponsive to conventional treatments. Patients were treated with PRGF eye drops (four times a day). Outcome measures were ocular surface disease index (OSDI), best-corrected visual acuity (BCVA, in logarithm of the minimum angle of resolution), visual analog scale (VAS), frequency and severity of symptoms, and IOP. The safety of the treatment was also evaluated., Results: Six patients (seven eyes with open-angle glaucoma and one eye with uveitic glaucoma) treated with PRGF eye drops were evaluated. Mean age was 71 years (SD=7.2, range 58-79 years). Five were female and one was male. The mean treatment time was 21.8 weeks (SD=9.0, range 12-36 weeks). The mean time to reach closure of the corneal ulcer was 14.5 (SD=5.5) weeks. A statistical significant reduction in OSDI scale (50.6%), VAS frequency (53.1%), VAS severity (42.0%), and a 41.8% improvement in BCVA were observed ( p <0.05). IOP also decreased by 16.6% ( p =0.010). Only one of the six patients reported itching in both eyes as an adverse event (AE); however, the patient continued with the PRGF eye drops until the end of therapy; the remaining patients did not report any AEs during the follow-up period., Conclusions: In patients with glaucoma and secondary OSDs refractive to conventional treatments, the treatment with PRGF eye drops could be considered a possible therapeutic option, because it demonstrates an improvement in the signs and symptoms of the ocular surface, as well as a better control of the IOP. This is an initial research work that can open doors for future research to confirm these findings., Competing Interests: Disclosure The authors declare the following competing financial interest(s): EA is the Scientific Director of BTI Biotechnology Institute, GO and FM are scientists at BTI Biotechnology Institute, a dental implant company that investigates in the fields of oral implantology and PRGF-Endoret technology. The authors report no other conflicts of interest in this work.

Purpose: The aim of this study was to evaluate the use of plasma rich in growth factors (PRGF) eye drops in patients with dry eye disease after laser-assisted in situ keratomileusis (LASIK) surgery., Material and Methods: This is a longitudinal, retrospective, comparative, and descriptive study of 77 eyes of 42 patients with dry eye disease following LASIK surgery. This study was designed to evaluate the efficacy of PRGF treatment compared to conventional therapy (control group). Outcome measures including signs and symptoms of dry eye disease were evaluated before and after treatment. The percentage of change before and after treatment for each clinical variable measured was compared between both groups., Results: There were 1-4 treatment cycles with PRGF eye drops (1 cycle = 6 weeks). Results showed a statistically significant improvement in the Ocular Surface Disease Index (38.12%), visual analogue scale scores for frequency (41.89%) and severity (42.47%), and the Schirmer test scores (88.98%) after PRGF treatment (p < 0.05). No adverse events were reported after PRGF treatment., Conclusions: These results suggest that PRGF eye drops are effective for the improvement of dry eye symptoms in patients who underwent LASIK surgery in comparison to the conventional therapy. The treatment with PRGF is an alternative for patients who suffer from postoperative dry eye., (© 2018 S. Karger AG, Basel.)

Purpose: The objective was to provide preliminary information about the efficacy and safety of immunologically safe plasma rich in growth factor (immunosafe PRGF) eye drops in the treatment of moderate to severe dry eye in patients with primary and secondary Sjögren's syndrome (SS) and to analyze the influence of several variables on treatment outcomes., Methods: This retrospective study included patients with SS. All patients were treated with previously immunosafe PRGF eye drops to reduce the immunologic component contents. Ocular Surface Disease Index (OSDI) scale, best-corrected visual acuity (BCVA), visual analog scale (VAS) frequency, and VAS severity outcome measures were evaluated before and after treatment with immunosafe PRGF. The potential influence of some patient clinical variables on results was also assessed. Safety assessment was also performed reporting all adverse events., Results: Twenty-six patients (12 patients with primary SS, and 14 patients suffering secondary SS) with a total of 52 affected eyes were included and evaluated. Immunosafe PRGF treatment showed a significant reduction (P < 0.05) in OSDI scale (41.86%), in BCVA (62.97%), in VAS frequency (34.75%), and in VAS severity (41.50%). BCVA and VAS frequency scores improved significantly (P < 0.05) after concomitant treatment of PRGF with corticosteroids. Only 2 adverse events were reported in 2 patients (7.7% of patients)., Conclusions: Signs and symptoms of dry eye syndrome in patients with SS were reduced after treatment with PRGF-Endoret eye drops. Immunosafe PRGF-Endoret is safe and effective for treating patients with primary and secondary SS.

Atropine has been used for more than a century to arrest myopia progression. Compelling evidence of its protective effect has been reported in well-designed clinical studies, mainly performed during the last two decades. However, its exact mechanism of action has not been determined. Experimental findings have shown that the mechanism is not related to accommodation, as was thought for decades. A review of the published literature revealed a significant amount of evidence supporting its safety and efficacy at a concentration of 1.0%, and at lower concentrations (as low as 0.01%)., Competing Interests: Authors declared that the sponsors had not any role in the collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication. Therefore, this funding source had not any kind of influence (or bias) in the work. All the aforementioned authors met the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have provided approval for the revised manuscript to be published.

The use of blood derivatives represents an alternative therapeutic approach that is gaining interest in regenerative medicine due to its potential to stimulate and accelerate tissue healing. Autologous serum eye drops and platelet-enriched plasma eye drops are being used in the treatment of different ophthalmological disorders. In this review, we summarize the different blood-derived formulations used in the treatment and care of ocular surface disorders. The biological basis and use of autologous serum and plasma rich in growth factors are deeply evaluated as well as the challenges to be addressed in the future in this new generation of blood-derived therapies., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

A 40-year-old man presented to the emergency service of the Department of Ophthalmology, Fundación Oftalmológica de Santander, Floridablanca, Colombia, with blurred vision in his right eye. Anamnesis revealed that he also had newly diagnosed stage C HIV. He had recently started highly active antiretroviral therapy (HAART). Examination disclosed intraocular inflammation, along with plain white peripheral non-exudative lesions with sparse haemorrhaging. The differential diagnosis included cytomegalovirus (CMV) retinitis and immune recovery uveitis (IRU). On follow-up, the patient's left eye presented with decreased visual acuity and increased vitreous haze. A vitrectomy with vitreous tap was performed for microbiological studies. PCR for CMV in the vitreous sample was negative. The patient was discharged with the final diagnosis of IRU. In HIV patients with uveitis, the knowledge of characteristic signs and symptoms of particular entities such as opportunistic infections and IRU will enable the clinician to give the appropriate treatment., (2015 BMJ Publishing Group Ltd.)

A 59-year-old Hispanic woman presented with a 3-year history of floaters associated with bilateral reduced visual acuity. Her best-corrected visual acuity (BCVA) was 20/40. Both anterior segments were without inflammation, but fundoscopy showed mild vitreous inflammation and multiple inflammatory choroidal lesions. Tests for inflammatory and infectious diseases were negative except for human leucocyte antigen A29. The patient was diagnosed with birdshot choroidoretinopathy, and treatment was initiated with cyclosporine A 2.5 mg/kg/day. One year after treatment, the patient reported systemic symptoms with no improvement in visual acuity. Fundus findings remained with vitreal inflammation. QuantiFERON-TB Gold In-Tube Test was positive, and a diagnosis of presumed latent ocular tuberculosis (TB) was made. We initiated anti-TB treatment for 9 months. At 6 months of anti-TB therapy, there was no active inflammation. The patient was followed for 2 years with no medications and no active inflammation. Her final BCVA was 20/25., (2015 BMJ Publishing Group Ltd.)

Eye pain is an unpleasant sensory and emotional experience including sensory-discriminative, emotional, cognitive, and behavioral components and supported by distinct, interconnected peripheral and central nervous system elements. Normal or physiological pain results of the stimulation by noxious stimuli of sensory axons of trigeminal ganglion (TG) neurons innervating the eye. These are functionally heterogeneous. Mechano-nociceptors are only excited by noxious mechanical forces. Polymodal nociceptors also respond to heat, exogenous irritants, and endogenous inflammatory mediators, whereas cold thermoreceptors detect moderate temperature changes. Their distinct sensitivity to stimulating forces is determined by the expression of specific classes of ion channels: Piezo2 for mechanical forces, TRPV1 and TRPA1 for heat and chemical agents, and TRPM8 for cold. Pricking pain is evoked by mechano-nociceptors, while polymodal nociceptors are responsible of burning and stinging eye pain; sensations of dryness appear to be mainly evoked by cold thermoreceptors. Mediators released by local inflammation, increase the excitability of eye polymodal nociceptors causing their sensitization and the augmented pain sensations. During chronic inflammation, additional, long-lasting changes in the expression and function of stimulus-transducing and voltage-sensitive ion channels develop, thereby altering polymodal terminal's excitability and evoking chronic inflammatory pain. When trauma, infections, or metabolic processes directly damage eye nerve terminals, these display aberrant impulse firing due to an abnormal expression of transducing and excitability-modulating ion channels. This malfunction evokes 'neuropathic pain' which may also result from abnormal function of higher brain structures where ocular TG neurons project. Eye diseases or ocular surface surgery cause different levels of inflammation and/or nerve injury, which in turn activate sensory fibers of the eye in a variable degree. When inflammation dominates (allergic or actinic kerato-conjunctivitis), polymodal nociceptors are primarily stimulated and sensitized, causing pain. In uncomplicated photorefractive surgery and moderate dry eye, cold thermoreceptors appear to be mainly affected, evoking predominant sensations of unpleasant dryness.

Purpose: In this study, we investigated the wound-healing process after photorefractive keratectomy with mitomycin C (MMC) in hen corneas. In addition, we evaluated the synergistic effect of ethanol and MMC., Methods: Forty-eight adult hens were divided into 3 groups: A: ethanol-assisted debridement plus MMC; B: mechanical debridement plus MMC; and C: mechanical debridement (MMC-untreated control). Photorefractive keratectomy was performed, and the animals were followed up for up to 60 days. Epithelial healing was measured with fluorescein. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end-labeling assay and proliferation was measured by BrdU incorporation. Both myofibroblast differentiation and collagen deposition were evaluated by immunofluorescence and histology., Results: Epithelial wound closure was similar in all 3 groups (P > 0.05). Significant reduction in haze was observed in groups A and B compared with C (P < 0.01), but there was no difference between groups A and B (P > 0.05). Furthermore, there was no difference in the number of apoptotic cells between groups. Proliferation was delayed in both groups A and B compared with C (P < 0.01), but groups A and B did not differ significantly (P > 0.05). Myofibroblasts, cellular density, and collagen deposition were lower in both groups A and B compared with C (P < 0.01), but they were not significantly different from each other (P > 0.05)., Conclusions: Topical application of MMC in hen corneas reproduces the wound healing observed in humans by reducing haze, keratocyte proliferation, myofibroblast differentiation, and new collagen deposition. Synergistic cytotoxic effects of ethanol and MMC were not observed.

Purpose: Nerve growth factor (NGF) is a neuropeptide essential for the development, survival, growth, and differentiation of corneal cells. Its effects are mediated by both TrkA and p75 receptors. Clinically relevant use of NGF was introduced to treat neurotrophic ulcerations in patients. Herein, we examine the mechanisms by which NGF enhances epithelial wound healing both in vivo and in vitro., Methods: An animal model using adult hens was implemented for the in vivo experiments. Laser ablation keratectomy was performed and animals were observed for up to 7 days. Epithelial healing was measured with fluorescein. In addition, proliferation was measured using BrdU incorporation and both TrkA and matrix metalloprotease-9 (MMP-9) expression were measured by immunohistochemistry (IHC) and Western blot (WB). In vitro experiments were carried out with telomerase-immortalized human corneal epithelial cells (HCLE). The rate of proliferation was measured using a colorimetric assay and BrdU incorporation. Real-time migration was evaluated with an inverted microscope. MMP-9 expression was evaluated by immunocytochemistry (ICC), WB, zymography, and RT-PCR. Finally, beta-4 integrin (β4) expression was assessed by ICC and WB., Results: Faster epithelial healing was observed in NGF-treated corneas compared with controls (P < 0.01). These corneas showed increased proliferation, TrkA upregulation, and enhanced MMP-9 presence (P < 0.01). In vitro, faster spreading and migration were observed in response to NGF (P < 0.01). Enhanced proliferation, as well as enhanced TrkA and MMP-9 expression, and decreased β4 levels were observed after adding NGF (P < 0.01)., Conclusions: NGF plays a major role during the epithelial healing process by promoting migration, a process that is accelerated by cell spreading. This effect is mediated by both the upregulation of MMP-9 and cleavage of β4 integrin.

Purpose: To assess the visual and refractive outcomes of implantation of intrastromal corneal ring segments (ICRS) in keratoconic eyes with no coincident topographic and comatic axes., Methods: Forty-one keratoconic eyes of 39 patients with no coincident topographic and comatic axes were implanted inferiorly with a Ferrara-type ICRS (Keraring SI6; Mediphacos Inc., Belo Horizonte, Brazil) of 150° of arc with a thickness of 150, 200, and 250 μm. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), corneal coma-like root mean square, and residual refractive errors analyzed using vector analysis were recorded before and 6 months after the ICRS implantation., Results: Mean UDVA was 0.76 ± 0.41 logMAR before and 0.53 ± 0.46 logMAR after surgery (P = .0006). CDVA was 0.13 ± 0.14 logMAR before and 0.07 ± 0.09 logMAR after surgery (P = .0007). Two eyes (4.9%) lost two lines or more of CDVA, 3 eyes (7.32%) lost one line, 16 eyes (39.02%) had no change in CDVA, 9 eyes (21.95%) gained one line, and 11 eyes (26.83%) gained two lines or more of CDVA. The safety index was 1.10. Spherical equivalent was significantly reduced after ICRS implantation (P < .001). Corneal coma-like root mean square changed from 0.80 ± 0.53 μm before surgery to 0.61 ± 0.59 μm after surgery (P = .02) for 4.5 mm of pupil size., Conclusions: One Ferrara-type ICRS of 150° of arc with a thickness of 150, 200, or 250 μm implanted inferiorly may reduce both astigmatism and corneal coma-like aberrations in keratoconic eyes with no coincident topographic and comatic axes, providing an improvement of UDVA and CDVA values., (Copyright 2013, SLACK Incorporated.)

Acanthamoeba keratitis is a serious pathogenic corneal disease, with challenging diagnosis. Standard diagnostic methods include corneal biopsy (involving cell culture) and in vivo reflection corneal microscopy (in which the visualization of the pathogen is challenged by the presence of multiple reflectance corneal structures). We present a new imaging method based on fluorescence sectioned microscopy for visualization of Acanthamoeba. A fluorescent marker (MT-11-BDP), composed by a fluorescent group (BODIPY) inserted in miltefosine (a therapeutic agent against Acanthamoeba), was developed. A custom-developed fluorescent structured illumination sectioned corneal microscope (excitation wavelength: 488 nm; axial/lateral resolution: 2.6 μm/0.4-0.6 μm) was used to image intact enucleated rabbit eyes, injected with a solution of stained Acanthamoeba in the stroma. Fluorescent sectioned microscopic images of intact enucleated rabbit eyes revealed stained Acanthamoeba trophozoites within the stroma, easily identified by the contrasted fluorescent emission, size and shape. Control experiments show that the fluorescent maker is not internalized by corneal cells, making the developed marker specific to the pathogen. Fluorescent sectioned microscopy shows potential for specific diagnosis of Acanthamoeba keratitis. Corneal confocal microscopy, provided with a fluorescent channel, could be largely improved in specificity and sensitivity in combination with specific fluorescent marking.

Purpose: To evaluate the efficacy, predictability, and safety of implantation of Ferrara-type intrastromal corneal ring segments (ICRS) for refractive correction of paracentral keratoconus., Setting: Fernández-Vega Ophthalmological Institute, Oviedo, Spain., Design: Cohort study., Methods: Snellen uncorrected (UDVA) and corrected (CDVA) distance visual acuities and residual refractive errors were recorded before and 6 months after ICRS implantation for keratoconus. The tunnels for ICRS implantation were created with a femtosecond laser. The power vector and the Alpins method were used to analyze postoperative refractive outcomes., Results: The study evaluated 56 eyes of 49 patients. The mean UDVA was 0.17 ± 0.14 (SD) preoperatively and 0.41 ± 0.28 postoperatively and the mean CDVA, 0.70 ± 0.18 and 0.80 ± 0.17, respectively (both P<.0001). The efficacy index was 0.60. Five eyes lost 1 line of CDVA, 17 eyes had unchanged CDVA, 15 eyes gained 1 line, 9 eyes gained 2 lines, 7 eyes gained 3 lines, and 3 eyes gained 4 lines. The safety index was 1.14. The spherical equivalent and astigmatism were significantly lower postoperatively than preoperatively (P<.01). Of the eyes, 78.6% were within ±1.00 D of the target-induced astigmatism. No intraoperative or postoperative complications occurred., Conclusion: Intrastromal corneal ring segment implantation in eyes with paracentral keratoconus provided good visual and refractive outcomes, indicating that it is a predictable and safe procedure for refractive correction in these cases., (Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: Plasma rich in growth factors (PRGF-Endoret) technology is an autologous platelet-enriched plasma obtained from patient's own blood, which after activation with calcium chloride allows the release of a pool of biologically active proteins that influence and promote a range of biological processes including cell recruitment, and growth and differentiation. Because ocular surface wound healing is mediated by different growth factors, we decided to explore the potential of PRGF-Endoret technology in stimulating the biological processes related with fibroblast-induced tissue repair. Furthermore, the anti-fibrotic properties of this technology were also studied., Methods: Blood from healthy donors was collected, centrifuged and, whole plasma column (WP) and the plasma fraction with the highest platelet concentration (F3) were drawn off, avoiding the buffy coat. Primary human cells including keratocytes and conjunctival fibroblasts were used to perform the "in vitro" investigations. The potential of PRGF-Endoret in promoting wound healing was evaluated by means of a proliferation and migration assays. Fibroblast cells were induced to myofibroblast differentiation after the treatment with 2.5 ng/mL of TGF-β1. The capability of WP and F3 to prevent and inhibit TGF-β1-induced differentiation was evaluated., Results: Results show that this autologous approach significantly enhances proliferation and migration of both keratocytes and conjunctival fibroblasts. In addition, plasma rich in growth factors prevents and inhibits TGF-β1-induced myofibroblast differentiation. No differences were found between WP and F3 plasma fractions., Conclusions: These results suggest that PRGF-Endoret could reduce scarring while stimulating wound healing in ocular surface. F3 or whole plasma column show similar biological effects in keratocytes and conjunctival fibroblast cells.

Purpose: Understanding corneal biomechanics is important to refractive or therapeutic corneal treatments. The authors studied the corneal response to variable intraocular pressure (IOP) in porcines eyes after UV collagen cross-linking (CXL), in comparison with untreated eyes., Methods: Twenty-three enucleated eyes were treated with standard CXL conditions (365 nm, 3 mW, 30 minutes), and 15 contralateral eyes served as control. Eyes (within a humidity- and temperature-monitored wet chamber) were measured by Scheimpflug corneal three-dimensional topographer. Images were obtained automatically while IOP either remained constant (14 eyes) or increased (24 eyes) by 40 mm Hg and then decreased (4-mm Hg steps). Measurements were performed immediately after treatment and 24 hours later. Corneal geometry was analyzed as a function of IOP, and whole globe stress-strain curves were calculated., Results: Instillation of riboflavin-dextran solution reduced corneal thickness (by 281 +/- 5 microm). Cross-linking produced a 1.54x reduction in corneal thinning and 2.8x reduction in corneal apical rise with increased IOP. Anterior and posterior cornea flattened with increased IOP (less flattening in CXL eyes) and became steeper with decreased IOP. The horizontal meridian flattened significantly (P < 0.01) more than the vertical meridian. Young's modulus was higher in cross-linked eyes (1.096 +/- 0.30 kN/m(2)) than in non-cross-linked eyes (0.692 +/- 0.30 kN/m(2)). Hysteresis in nontreated eyes was also larger than in cross-linked eyes., Conclusions: Cross-linking stiffened porcine corneas significantly. Both experimental data and stress-strain analysis are valuable for finite element models to improve understanding of CXL and its predictability. Although differences are expected between human corneas in vivo and porcine corneas ex vivo, the results are consistent with clinical data found in patients. The apparent biomechanical anisotropy of pig corneas must be confirmed in humans.

Purpose: To determine the relation between the corneal light transmission measurements and the epithelial surface properties in hen corneas after different refractive surgery techniques photorefractive keratectomy, laser in situ keratomileusis, and laser-assisted subepithelial keratomileusis, and a group with only epithelial corneal removal (deepithelialization)., Methods: Five groups of hen corneas with different treatments and a control group were analyzed at 30 days. Direct transmittance and corneal light scattering were measured by a scatterometer developed by our group. Quantitative and systematic measurements of external and internal roughness and epithelium thickness were assessed using standard techniques developed for quantitative analysis of microphotographs of the corneal epithelium., Results: Data analysis revealed that the roughness in the epithelial surface was associated with the corneal light transmission. The direct transmittance of light showed a significant correlation with the epithelial roughness in the control (r = -0.99, p < 0.05) and photorefractive keratectomy (r = -0.99, p < 0.05) groups. However, there was no relation between the epithelial thickness and the corneal light transmission measurements., Conclusions: The experimental results suggested that the roughness of the epithelial surfaces is related to the light transmission in the cornea.

Purpose: Polymethylmethacrylate (PMMA) segments are normally used in additive surgery to treat both corneal ectasia post laser-assisted in situ keratomileusis and keratoconus. The aim of this work was to develop an experimental animal model to induce wound healing in the deep stroma in corneas of hens., Methods: PMMA segments were implanted in the right eyes of 40 adult hens without suture in the wound incision. Animals were randomized for 5 time points to histopathology study (1, 3, 15, 30, and 90 days) being clinically evaluated during the experiment., Results: Thirty-four eyes (85%) had a successful clinical outcome and intraoperative mistakes occurred in 6 eyes (15%), including anterior chamber perforation resulting in abscess (1), excess of lamellar dissection with segment migration (3), and peripheral incisions evolving with neovascularization (2). At 24 hours, all the epithelial injuries were completed in integrity, but a persistent stromal incision, with a fish mouth form, was observed until day 15. Corneal edema disappeared at the fifth day. Haze, keratocyte cell death, keratocyte proliferation, myofibroblast differentiation, and new matrix production were observed in length around the segment., Conclusions: Wound healing was induced in the deep corneal stroma by means of PMMA segment implantation in a new animal model developed in hens.

Purpose: To validate the estimation of corneal aberrations from videokeratography against a laser ray tracing technique that measured total eye aberrations, in eyes without keratoconus (ie, cornea-dominated wave aberrations)., Methods: We measured total and corneal wave aberrations of three eyes diagnosed with keratoconus by slit-lamp microscopy and corneal topography: two eyes from one patient with early keratoconus and one eye with more advanced keratoconus. Total aberrations were measured with laser ray tracing. Corneal aberrations were obtained from corneal elevation data measured with a corneal videokeratoscope using custom software that performs virtual ray tracing on the measured front corneal surface., Results: The keratoconus eyes showed a dramatic increase in aberrations (both corneal and total) particularly coma-like terms, which were 3.74 times higher on average than normal. Anterior corneal surface aberrations and total aberrations Were similar in keratoconus. This similarity was greater for the early keratoconus patient, suggesting a possible implication of the posterior corneal surface in advanced keratoconus., Conclusions: The similarity found between corneal and total aberration patterns in keratoconus provided a cross-validation of both types of measurements (corneal topography and aberrometry). Both techniques were useful in diagnosing and quantifying optical degradation imposed by keratoconus.