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BACKGROUND: Low-level laser therapy (LLLT) and human amniotic membrane (HAM) application have been shown to be viable options for use in wound healing. PURPOSE: This study sought to compare LLLT and HAM to a control treatment (hydrogel, saline, and gauze) in persons with diabetes mellitus (DM) and foot ulcers. METHODS: Using a prospective pilot clinical study design, patients receiving care at a health center that specializes in the treatment of diabetic foot wounds between November 2016 and August 2017 were recruited. Eligible patients had to be 30 to 59 years of age; diagnosed with type 2 DM (postprandial capillary glucose levels between 140 and 350 mg/dL); and have uninfected, granulating stage 2 or 3 foot ulcers measuring less than 7 cm by 3 cm. Immunosuppressed and malnourished patients or those with neoplasms or in critical condition were not eligible to participate. Patients received the control treatment (2 mg hydrogel, saline, and gauze), HAM (patches of thawed HAM, applied with overlapping edges), or LLLT (phototherapy session, 2 mg hydrogel, saline, and gauze) for 28 days. Variables, wound area measurements, Pressure Ulcer Scale for Healing (PUSH) scores, and Visual Analog Scale (VAS) scores were used to assess wound improvement progress and pain on days 7, 14, 21, and 28. Descriptive statistics were used to analyze the participant anthropometric and clinical profiles. The Kolmogorov-Smirnov test was used to analyze the sample distribution. The Kruskal-Wallis test with Dunn’s post-test was used to evaluate differences in PUSH and VAS scores and wound size for intergroup analysis, and the Mann-Whitney U test was used for the same outcomes in intragroup analysis. The level of significance was 5% (P < .05). RESULTS: Twenty-seven (27) patients participated (mean age, 51.4 years; mean body mass index, 26.5 kg/m2), with 9 patients in each treatment group. No statistically significant differences were noted in clinical or anthropometric variables among the groups, but mean baseline wound areas were different (2.6 cm² for the control, 1.9 cm² for the LLLT, and 5.5 cm² for the HAM groups). Intragroup comparisons showed a significant reduction in PUSH score in the LLT group between days 0 and 21 (8.2 vs 4.9; P < .01) and days 21 to 28 (4.9 vs 3.2; P < .001). In all treatment groups the percent reduction was significantly different between days 7 and 28. No outcomes were significantly different between groups. CONCLUSION: Diabetic foot ulcer wound area as well as PUSH and VAS scores showed more improvement for patients with DM receiving LLLT or HAM than for the control group, but the differences were not significant. Larger studies are needed to compare these treatment modalities.

The ocular surface is exposed continuously to the environment and, as a consequence, to a variety of different microbes. After the results of the Human Microbiome Project became publicly available, international research groups started to focus interest on exploring the ocular surface microbiome and its physiopathological relationship to the eye. For example, numerous research studies the existence of the ocular surface's bacterial flora, typically gathering cultures from healthy patients and finding few variations in the bacterial species. More recently, culture-independent methods, including 16S ribosomal ribonucleic acid (rRNA) gene sequencing, are being used to define the ocular microbiome. These newer methods suggest that the microbial communities have a greater diversity than previously reported. These communities seem to serve an immune-modulating function and maintain relationships with other microbes and organs, even distant ones. This review summarizes the literature exploring the ocular microbiome, both in health and in different diseases.

Purpose In recent decades, the medical and surgical treatment of limbal stem cell deficiency (LSCD) has evolved significantly through the incorporation of innovative pharmacological strategies, surgical techniques, bioengineering, and cell therapy. With such a wide variety of options, there is a need to establish a global consensus on the preferred approaches for the medical and surgical treatment of LSCD. Methods An international LSCD Working Group was established by the Cornea Society in 2012 and divided into subcommittees. Four face-to-face meetings, frequent email discussions, and teleconferences were conducted since then to reach agreement on a strategic plan and methods after a comprehensive literature search. A writing group drafted the current study. Results A consensus in the medical and surgical management of LSCD was reached by the Working Group. Optimization of the ocular surface by eyelid and conjunctival reconstruction, antiinflammatory therapy, dry eye and meibomian gland dysfunction treatment, minimization of ocular surface toxicity from medications, topical medications that promote epithelialization, and use of a scleral lens is considered essential before surgical treatment of LSCD. Depending on the laterality, cause, and stage of LSCD, surgical strategies including conjunctival epitheliectomy, amniotic membrane transplantation, transplantation of limbal stem cells using different techniques and sources (allogeneic vs. autologous vs. ex vivo-cultivated), transplantation of oral mucosal epithelium, and keratoprosthesis can be performed as treatment. A stepwise flowchart for use in treatment decision-making was established. Conclusions This global consensus provides an up-to-date and comprehensive framework for the management of LSCD.

Purpose Dry eye is a common, complex, and multifactorial disease of the ocular surface and tear film that results in discomfort and visual disturbances. Prevalence rates vary and largely rely on studies involving older populations. This study sought to evaluate dry eye among a sample of young students in Brazil. Methods Cross-sectional survey included 2,140 students using 2 self-applicable questionnaires of dry eye symptoms: the Ocular Surface Disease Index (OSDI) and the Women’s Health Study (WHS) questionnaire and a list of risk factors associated with dry eye. Participants with dry eye symptoms underwent a clinical evaluation. Results Participants were 23.4±5.2 years of age, 56.1% female and 43.9% male, 34.4% had an OSDI score greater than 22, and 23.5% had dry eye according to the WHS. Dry eye frequency differed consistently between the sexes: 42.6% women and 24.0% men based on the OSDI, and 27.1% women and 18.5% men based on the WHS. Univariate and multivariate analyses demonstrated that female sex, contact lens wear, the screen use for more than 6 hours per day, less than 6 hours of sleep a night, and certain medications were relevant related risk factors for dry eye. Despite symptoms, clinical evaluations demonstrated mild signs of dry eye. Conclusions Dry eye symptoms were found to be a prevalent condition among Brazilian undergraduate students. Compared to the rates of dry eye among the general Brazilian population over 40 years of age, students present at higher dry eye symptoms rates and distinct odds for related risk factors were identified.

Ex vivo cultivation and transplantation of limbal epithelial cells has been reported as an alternative source for ocular surface reconstruction. However, until now, the functional improvement of these patients is limited due to the low survival rate of the transplanted cells. Consequently, the clinical benefits of this therapeutic strategy are only temporary and can assign them to paracrine effects associated with the transplanted cells. With this background in mind, we aimed to analyze the effect of different conditioned media containing growth factors secreted by limbal progenitor cells on corneal epithelial healing, both in vitro and in vivo. Limbal tissue was used to obtain different conditioned media (CM). For the in vitro assay, corneal epithelial cells were treated with CM and the epithelial migration was analyzed. Growth factors in the CM were identified with ELISA and multiplex. For the in vivo assay in rats, total limbal stem cell deficiency (LSCD) was induced with an abrasive injury to the ocular surface, and the animals were treated with different CM. Clinical and histological analyses were performed. In the in vitro assay, treatment with limbal fibroblast (LF CM) was more effective compared to the other CM, and analysis revealed high concentrations of keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF). In the in vivo assay, animals treated with LF CM showed epithelial defect improvement, maintenance of thickness, and decreased opacity and neovascularization. This treatment also allowed better ocular surface tissue organization when compared to the other treatments. The in vitro and in vivo experiments showed better outcomes in the corneal wound healing for the LF CM treatment. The high concentrations of KGF and HGF, linked to epithelial cell migration and proliferation, may correlate to the best results found in this treatment.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute and potentially fatal inflammatory vesiculobullous reactions that affect the skin and mucous membranes, and which are most often triggered by particular medications and infections. In Brazil, the drugs most frequently associated with TEN and SJS include cold medicine such as dipyrone and NSAIDs, followed by carbamazepine, phenobarbital, penicillin, and allopurinol. Genetic variations have been found to increase the risk of SJS/TEN in response to triggering factors such as medications. The most closely associated genes found in Brazilian cold-medicine-related SJS/TEN patients with severe ocular complications are HLA-A*66:01 in those of mixed African and European ancestry and HLA-B*44:03 and HLA-C*12:03 in those of solely European ancestry. Our classification system for grading ocular surface complication severity in SJS/TEN patients revealed the most severe complications to be limbal stem cell deficiency and dry eye. Changes to the conjunctival flora have also been observed in SJS/TEN patients. Our group identified bacterial colonization in 95% of the eyes (55.5% of which were gram-positive cocci, 25.5% of which were gram-negative bacilli, and 19% of which were gram-positive bacilli). Several new treatment options in the acute and chronic ocular management of the SJS/TEN patients have been described. This article highlights some Brazilian institutions' contributions to ocular surface care in both the acute phase (including the use of amniotic membrane transplantation) and the chronic phase (such as eyelid margin and fornix reconstruction, minor salivary gland transplantation, amniotic membrane and limbal transplantation, scleral contact lenses, anti-angiogenic eyedrops for corneal neovascularization, ex-vivo cultivated limbal epithelium transplantation, conjunctival-limbal autografting, oral mucosa transplantation, and keratoprosthesis).

PURPOSE To describe the outcomes of Descemet membrane endothelial keratoplasty (DMEK) performed by cornea fellows during their initial learning curve. METHODS This prospective study included the first consecutive series of 53 DMEK surgeries performed by 14 corneal fellows at Sorocaba's Ophthalmological Hospital. Best spectacle-corrected visual acuity, endothelial cell density (ECD), and complications were evaluated. RESULTS Of the eyes without ocular comorbidities and with complete visual acuity measurements, 97% of 33 eyes achieved a best spectacle-corrected visual acuity of ≥20/40 in 6 months. The mean (SD) preoperative donor ECD was 2453 (361) cells/mm, and at 6 months postoperatively, the in vivo mean ECD (SD) was found to be 1300 (587) cells/mm, an average loss of 47%. Preparation of the DMEK graft by the cornea fellows was successful in all cases. There were 9 eyes (17%) that experienced partial graft detachment requiring rebubbling. A total of 3 eyes (5.7%) failed to clear the cornea, all of which were managed with successful secondary endothelial keratoplasty. None of the eyes experienced pupillary block. CONCLUSIONS Establishing DMEK in a fellowship program was successful with the supervision of an experienced DMEK surgeon. Even without the facility of a prestripped DMEK graft by an eye bank and with no backup tissue, no surgery was canceled because of graft preparation failure. Good visual outcomes were achieved with satisfactory ECD at 6-month follow-up, with an acceptable complication rate. Even the 3 eyes that failed to clear the cornea evolved well after secondary endothelial keratoplasty by the cornea fellows.

Several aspects of the quality of life (QoL) and treatment satisfaction of patients with dry eye disease (DED) may be underestimated. Ocular symptoms, which are assessed by validated patient-reported questionnaires and may include stinging, burning, itchiness, grittiness, dryness and discomfort, reduce QoL by affecting daily activities and work productivity. Self-reported symptoms do not always correlate with post-treatment improvements in clinical measures such as tear film break-up time, inflammation and osmolarity. Thus, treatments may improve clinical ocular features without improving symptoms that affect daily life. This review explores 1500 abstracts from congress presentations and peer-reviewed journals for QoL and treatment satisfaction data on the use of active lubricants, osmoprotectants, secretagogues, and immunomodulators present in topical formulations for DED treatment, and validated symptom questionnaires. Patient-reported symptoms of DED are generally improved after treatment with topical formulations for tear replacement, tear stimulation or anti-inflammatory therapy compared with baseline or a control treatment. However, more data are required to compare the performance of active ingredients. It is fundamental to diagnose patients with DED accurately, recognising the major cause behind their dry eyes. Studies are also necessary to identify how patient satisfaction and QoL may be improved through long-term use of topical preparations. We conclude that careful and thorough consideration of patient-reported symptoms should be integrated into DED management to help tailor treatment to patient needs.

The mission of the Tear Film & Ocular Surface Society (TFOS) is to advance the research, literacy, and educational aspects of the scientific field of the tear film and ocular surface. Fundamental to fulfilling this mission is the TFOS Global Ambassador program. TFOS Ambassadors are dynamic and proactive experts, who help promote TFOS initiatives, such as presenting the conclusions and recommendations of the recent TFOS DEWS II™, throughout the world. They also identify unmet needs, and propose future clinical and scientific solutions, for management of ocular surface diseases in their countries. This meeting report addresses such needs and solutions for 25 European countries, as detailed in the TFOS European Ambassador meeting in Rome, Italy, in September 2019.

The purpose of this study was to evaluate the feasibility of treating aniridia-associated keratopathy with a nonpenetrating artificial cornea in 2 patients with corneal blindness secondary to aniridia.This was a prospective, nonrandomized, interventional study of 2 consecutive patients with corneal blindness caused by aniridia. Ophthalmological examination was performed before the nonpenetrating keratoprosthesis surgery and then repeated 1, 7, 15, 30, 90, and 180 days and subsequently every 90 days thereafter. Optical coherence tomography was performed 90 days postsurgery to assess the position of the implant.Visual acuity improved significantly after the KeraKlear surgery. Postoperative findings included periprosthetic corneal thinning, neovascularization, and retroprosthetic opacity.KeraKlear nonpenetrating artificial corneas represent a promising alternative to keratolimbal allografts and Boston keratoprosthesis for the treatment of aniridia-associated keratopathy.

Purpose To determine whether corneal cross-linking (CXL) with individualized fluence (“sub400 protocol”) is able to stop keratoconus (KC) progression in ultrathin corneas with 12-month follow-up. Design Retrospective, interventional case series. Methods Thirty-nine eyes with progressive KC and corneal stromal thicknesses from 214 to 398 μm at the time of ultraviolet irradiation were enrolled. After epithelium removal, ultraviolet irradiation was performed at 3 mW/cm2 with irradiation times individually adapted to stromal thickness. Pre- and postoperative examinations included corrected distance visual acuity (CDVA), refraction, Scheimpflug, and anterior segment optical coherence tomography imaging up to 12 months after CXL. Outcome measures were arrest of KC progression at 12 months postoperatively and stromal demarcation line (DL) depth. Results Thirty-five eyes (90%) showed tomographical stability at 12 months after surgery. No eyes showed signs of endothelial decompensation. A significant correlation was found between DL depth and irradiation time (r = +0.448, P = .004) but not between DL depth and change in Kmax (r = −0.215, P = .189). On average, there was a significant change (P Conclusions The “sub400” individualized fluence CXL protocol standardizes the treatment in ultrathin corneas and halted KC progression with a success rate of 90% at 12 months. The sub400 protocol allows for the treatment of corneas as thin as 214 μm of corneal stroma, markedly extending the treatment range. The DL depth did not predict treatment outcome. Hence, the depth is unlikely related to the extent of CXL-induced corneal stiffening but rather to the extent of CXL-induced microstructural changes and wound healing.

Purpose: To report a case series of pterygium surgery with conjunctival autograft fixation using bipolar electrocautery. Design: A noncomparative, retrospective, interventional case series of pterygium surgery with follow-up longer than 12 months to assess recurrence and other complication rates. Participants: Fifty-six eyes of 37 patients were treated between April 2011 and January 2018, either for primary ( n = 53 cases) or recurrent ( n = 3 cases) pterygia. Intervention: After pterygium excision, free conjunctival grafts from the inferior bulbar conjunctiva of the same eye were harvested and fixated with the use of bipolar electrocautery. Main outcome measure: Recurrence of the pterygium and complications. Results: The mean follow-up was 41 months (range 12 to 81 months). There were no intraoperative complications. Recurrence of the lesion was seen in three eyes (5.36%). There were no other postoperative complications such as graft detachment, or formation of dellen or granulomas. Conclusion: Conjunctival autograft fixation using bipolar electrocautery seems to be a fast, costly and safe procedure that can be applied in most cases of pterygium surgery.

PURPOSE To describe the outcomes of Descemet membrane endothelial keratoplasty (DMEK) performed in amblyopic aged (younger than 8 years) children. METHODS This is a single-center retrospective study, including 11 eyes (7 congenital hereditary endothelial dystrophy and 4 congenital glaucoma) of 6 children in amblyopic age undergoing DMEK by a single surgeon (N.C.P.) at Sorocaba Eye Hospital from December 2015 to November 2017. Best spectacle-corrected visual acuity, biomicroscopy, pachymetry, endothelial cell density, and complications were evaluated. RESULTS No intraoperative complications occurred. Graft detachment occurred in 1 eye (9.1%) and was successfully managed with rebubbling. No primary graft failure or pupillary block was observed. All pachymetric measurements improved, and the corneal edema clinically resolved in all eyes within 2 weeks after the procedure. At the last follow-up (mean 30 months), best spectacle-corrected visual acuity was ≥20/40 in 7 (77.8%) of 9 eyes from patients cooperative enough to assess vision. All children began visual stimulation therapy and amblyopic treatment within 1 month of surgery, and all grafts remained clear until the last follow-up. The mean preoperative donor endothelial cell density was 2588 ± 236 cells/mm, which decreased to 1726 ± 292 cells/mm 2 years after surgery, yielding a 33% reduction (P < 0.001). No immunologic graft reaction, secondary graft failure, or cataracts were observed during the follow-up period. CONCLUSIONS In this series, DMEK was performed to successfully treat endothelial dysfunction in children. However, the procedure is more challenging, and more studies with more patients and longer follow-up are needed to confirm the superiority of DMEK in treating endothelial dysfunction in children.

Over the past 2 decades, posterior lamellar keratoplasty (PLK) has emerged as an alternative to penetrating keratoplasty in the treatment of corneal endothelial disorders. The reasons for this trend include the search for a safer procedure to replace diseased endothelium that provides faster and better visual rehabilitation and reduces the need for postoperative care. Different surgical techniques, surgical instruments, devices, and lasers have been introduced to overcome technical difficulties, thus improving clinical outcomes. Yet, surgeons and eye banks must address the complications and limitations that arise during the transition to these new techniques. This review discusses the most significant aspects of the evolution of PLK, including a detailed description of current techniques and the direction of future treatment for corneal endothelial disease with the use of laser-assisted surgery, bioengineered corneas, cell therapy, and new pharmacologic therapy.

Any prescribed or self-administered therapy carries inherent risks of secondary adverse events. While the volume of treatments being administered through healthcare systems has been increasing, scientific advancements in our understanding of the mechanisms of pharmaceutical side effects and complications from procedures now allow us to reduce the risk of non-intentional damage to ocular health. This review summarizes the most common and leading causes of iatrogenic visual impairment, corneal diseases, and conditions that present in a general ophthalmologic practice, including a comprehensive analysis of their pathophysiology and recommendations for management and prophylaxis.Iatrogenic corneal diseases and conditions can arise from topical drugs, contact lens use, eye surgeries and procedures, systemic drugs, non-ophthalmological events, and cosmetic procedures. Topical and systemic drugs may disturb tear film homeostasis or result in ocular surface deposits. The use of ill-fitted contact lenses can trigger eye discomfort and poor hygiene conditions that can predispose to severe infections. Procedures to the eye may result in a variety of anatomical and functional complications that ophthalmologists should be aware of how to avoid or at least be prepared to manage if they occur. Even non-ophthalmological events such as non-invasive ventilation, radiation therapies and, immune-based conditions, or cosmetic procedures such as eyelash growth and fillers, can result in unwanted damage to the ocular surface.

Purpose Whether Bowman's layer is contributing to corneal biomechanics is subject to controversy: surgical techniques such as Small Incision Lenticule Extraction (SMILE) and Bowman's layer transplantation suggest a role, whereas experimental studies performed on whole-thickness corneas failed to show a role. Here, the elastic modulus of thin corneal lamellae was measured, so that the potential relative biomechanical contribution of Bowman's layer would be greater. Setting Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Switzerland; ELZA-Institute, Dietikon, Switzerland; Department of Ophthalmology, Philipps University of Marburg, Germany. Design Prospective experimental laboratory study. Methods Twenty-six healthy human corneas were stripped of Descemet's membrane and the endothelium for DMEK. Following epithelium removal, corneas were divided into two groups. In group 1, Bowman's layer was ablated with an excimer laser (20μm-thick,10mmOZ). In group 2, Bowman's layer was left intact. Then, a lamella was cut from the anterior cornea with an automated microkeratome. Elastic-viscoelastic material properties were analyzed by 2D-stress-strain extensometry between 0.03-0.70N. Results Mean lamella thickness was 160±37 μm in corneas with Bowman's layer, and 155±22 μm in corneas without. No significant differences between flaps with and without Bowman's layer were observed in the tangential E-modulus between 5-20% strain (11.5±2.9 vs 10.8±3.7kPa, p>0.278). Conclusions The presence or absence of Bowman's layer did not reveal a measurable difference in corneal stiffness. This may indicate that the removal of Bowman's layer during photorefractive keratotomy (PRK) does not represent a disadvantage to corneal biomechanics.

Background To determine the average amount of mechanical forces applied to the lids of keratoconus patients during eye rubbing. Methods Fifty-seven patients (41 male, 16 female, average age 34.8 years) with a clinically and topographically diagnosed keratoconus and a history of eye rubbing were prospectively asked to perform their individual eye rubbing movement on a high-precision balance. The type of eye-rubbing movement and the force applied, represented in newtons (N), were recorded and analyzed. Results We detected three different types of eye rubbing. Rubbing with the fingertip was most frequent (51%), followed by rubbing with the knuckle (44%) and rubbing with the fingernail (6%). Each type of eye rubbing showed different average forces, with knuckle type eye rubbing applying significantly more force (9.6 ± 6.3 N) on the lids than fingertip (4.3 ± 3.1 N) and fingernail (2.6 ± 3.3 N) types (p p = 0,016, respectively). Conclusions There were major variations in the force exerted on the lids, depending on the type of eye rubbing employed. This data will help determine the forces that need to be applied in future experimental eye rubbing models.

AimsTo evaluate the expression of β-galactoside-binding proteins galectin (Gal)-1 and Gal-3 in patients with keratoconus (KC) and postcorneal collagen cross-linking (CXL) treatment in vitro.MethodsTear fluid, cornea samples and conjunctival impression cytology specimens from control and KC patients were used to evaluate Gal-1 and Gal-3 expressions. Primary keratocytes were isolated by collagenase digestion from surgically removed corneas of five normal or KC human corneal buttons and cultured in Dulbecco’s modified eagle medium/Ham’s F12 medium supplemented with 2% fetal bovine serum. These cells were evaluated under two experimental conditions: control and submitted to the application of ultraviolet A light and riboflavin 0.1% (CXL) for 30 min.ResultsPatients with KC displayed increased levels of Gal-1 and Gal-3 in conjunctival epithelial cells compared with control. Furthermore, KC corneas were associated with intense expression of Gal-1 in the stroma, released by keratocytes. Ultrastructural analysis of keratocytes showed a marked increase of endogenous Gal-3 levels, but not Gal-1, in KC. In vitro, CXL induced significant release of Gal-1 in keratocyte supernatants (116±18 ng/mL, PConclusionGal-1 and Gal-3 represent new interesting KC biomarkers as revealed by their different expression patterns in KC and control corneal samples. CXL has an immunosuppressive effect on keratocytes by reducing the release of cytokines and MMPs and increased expression of anti-inflammatory protein Gal-1.

This article presents an Executive Summary of the conclusions and recommendations of the 10-chapter TFOS DEWS II report. The entire TFOS DEWS II report was published in the July 2017 issue of The Ocular Surface. A downloadable version of the document and additional material, including videos of diagnostic and management techniques, are available on the TFOS website: www.TearFilm.org.

Dry eye can be caused by a variety of iatrogenic interventions. The increasing number of patients looking for eye care or cosmetic procedures involving the eyes, together with a better understanding of the pathophysiological mechanisms of dry eye disease (DED), have led to the need for a specific report about iatrogenic dry eye within the TFOS DEWS II. Topical medications can cause DED due to their allergic, toxic and immuno-inflammatory effects on the ocular surface. Preservatives, such as benzalkonium chloride, may further aggravate DED. A variety of systemic drugs can also induce DED secondary to multiple mechanisms. Moreover, the use of contact lens induces or is associated with DED. However, one of the most emblematic situations is DED caused by surgical procedures such as corneal refractive surgery as in laser-assisted in situ keratomileusis (LASIK) and keratoplasty due to mechanisms intrinsic to the procedure (i.e. corneal nerve cutting) or even by the use of postoperative topical drugs. Cataract surgery, lid surgeries, botulinum toxin application and cosmetic procedures are also considered risk factors to iatrogenic DED, which can cause patient dissatisfaction, visual disturbance and poor surgical outcomes. This report also presents future directions to address iatrogenic DED, including the need for more in-depth epidemiological studies about the risk factors, development of less toxic medications and preservatives, as well as new techniques for less invasive eye surgeries. Novel research into detection of early dry eye prior to surgeries, efforts to establish appropriate therapeutics and a greater attempt to regulate and oversee medications, preservatives and procedures should be considered.

The removal and rate of recurrence of pterygium have been discussed for years. The disorder is highly associated with environmental factors, and recurrence rates can be unacceptably high and cannot be successfully predicted. New techniques and graft preparations and postoperative management strategies are helping to reduce the recurrence rates and provide an ocular surface that is near ideal for future cataract or refractive surgery. This review discusses the advantages and disadvantages of various treatment strategies.

PurposeTo compare amniotic membrane transplantation (AMT) associated with narrow-strip conjunctival autograft vs conjunctival autograft alone for the treatment of recurrent pterygium.MethodsIn this prospective consecutive interventional study, patients with recurrent pterygium were randomly divided into one of 2 groups; group 1: patients undergoing AMT associated with autologous conjunctival graft; and group 2: patients undergoing conjunctival autograft alone.ResultsOf the 80 operated eyes included in this study, 39 (group 1, mean patient age 52.1 ± 11.7 SD years) underwent AMT associated with narrow-strip conjunctival autograft and 41 (group 2, mean patient age 45.8 ± 12.9 SD years) underwent conjunctival autograft alone. In group 1, 6 eyes (15.4%) had grade 1 pterygium, 19 eyes (48.7%) had grade 2 pterygium, and 14 eyes (35.9%) had grade 3 pterygium. In the second group, 5 eyes (12.2%) had grade 1 pterygium, 18 eyes (43.9%) had grade 2 pterygium, and 14 eyes (35.9%) had grade 3 pterygium. No statistically significant difference was found between the 2 groups (p = 0.752). Of the 39 eyes in group 1, recurrent pterygium was observed in 7 cases (17.9%). However, of the 41 eyes in group 2, recurrent pterygium was observed in only 4 cases (9.75%). No statistically significant difference was found between the 2 groups (p = 0.2684).ConclusionsThe results of this study indicate that conjunctival autograft alone might be a better surgical choice for the treatment of recurrent pterygia than combining it with AMT; however, this second option provides a good surgical alternative in cases where little conjunctival donor tissue is available.

Members of the ASCRS Cornea Clinical Committee performed a review of the current literature on the corneal crosslinking (CXL) procedure for treating corneal ectasia. The members explored the data on the techniques currently in use and under investigation, including their advantages, safety profiles, risks, and cost analyses, compared with data on corneal transplantation. They concluded that CXL limits the progression of keratoconus, thus reducing the need for transplantation. They also found that compared with permitting the disease to progress naturally, CXL techniques carry significant and long-term cost and safety benefits, primarily by reducing the need for corneal transplantation. Studies of various CXL techniques (eg, epithelium-on treatment, changes in ultraviolet light parameters, riboflavin composition) continue with the ultimate goal of improving the procedure's safety and efficacy.

PURPOSE: Despite extensive knowledge gained over the last three decades regarding limbal stem cell deficiency (LSCD), the disease is not clearly defined, and there is lack of agreement on the diagnostic criteria, staging and classification system among treating physicians and research scientists working on this field. There is therefore an unmet need to obtain global consensus on the definition, classification, diagnosis and staging of LSCD. METHODS: A Limbal Stem Cell Working Group was first established by the Cornea Society in 2012. The Working Group was divided into subcommittees. Four face-to-face meetings, frequent email discussions and teleconferences were conducted since then to obtain agreement on a strategic plan and methodology from all the participants after a comprehensive literature search, and reached final agreement on the definition, classification, diagnosis and staging of LSCD. A writing group was formed to draft the current manuscript, which has been extensively revised to reflect the consensus of the Working Group. RESULTS: A consensus was reached on the definition, classification, diagnosis and staging of LSCD. The clinical presentation and diagnostic criteria of LSCD were clarified, and a staging system of LSCD based on clinical presentation was established. CONCLUSIONS: This global consensus provides a comprehensive framework for the definition, classification, diagnosis and staging of LSCD. The newly established criteria will aid in the correct diagnosis and formulation of an appropriate treatment for different stages of LSCD that will facilitate a better understanding of the condition, help with clinical management, research and clinical trials in this area.

The transparency and maintenance of corneal epithelial integrity are essential for its optical properties and, to preserve these characteristics, the epithelium undergoes continuous renewal. This renewal depends on the control of cell proliferation and differentiation mediated by mitogenic factors responsible for increasing mitoses and stimulating cellular migration. Cell-cell communication plays a pivotal role in epithelial healing process, and several cytokines and growth factors are involved in this process. Understanding the cross-talk and paracrine effects of these cytokines and growth factors released can help in the search for new therapeutic strategies to treat ocular surface diseases.

Stevens-Johnson syndrome (SJS) is an acute blistering disease of the skin and mucous membranes. Acute SJS leads to the acute inflammation of the ocular surface and chronic conjunctivitis. If not properly treated, it causes chronic cicatricial conjunctivitis and cicatricial lid margin abnormalities. Persistent inflammation and ulceration of the ocular surface with cicatricial complications of the lids leads to chronic ocular sequelae, ocular surface damage, and corneal scarring. The destruction of the glands that secrete the tear film leads to a severe form of dry eye that makes the management of chronic SJS difficult. The option that is routinely used for corneal visual rehabilitation, keratoplasty, is best avoided in such cases. We describe the management strategies that are most effective during the acute and chronic stages of SJS. Although treatments for acute SJS involve immunosuppressive and immunomodulatory therapies, amniotic membrane transplantation is also useful. The options for visual rehabilitation in patients with chronic SJS are undergoing radical change. We describe the existing literature regarding the management of SJS and highlight recent advances in the management of this disorder.

Our purpose is to comprehensively review the state of the art with regard to Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to improving the management of associated ocular surface complications. SJS and TEN are two ends of a spectrum of immune-mediated disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. Part I of this review focused on the systemic aspects of SJS/TEN and was published in the January 2016 issue of this journal. The purpose of Part II is to summarize the ocular manifestations and their management through all phases of SJS/TEN, from acute to chronic. We hope this effort will assist ophthalmologists in their management of SJS/TEN, so that patients with this complex and debilitating disease receive the best possible care and experience the most optimal outcomes in their vision and quality of life.

To evaluate cytokine concentrations in amniotic membrane (AM) preserved in different preservation media, temperatures, and times and to compare them with those in fresh AM.Placentas were harvested from 8 women undergoing cesarean delivery, with each then divided into 17 pieces for the following preservation methods: at 2 different temperatures (-80 and 0°C), in 2 different preservation media (dimethyl sulfoxide and enriched TC199; Ophthalmos), and for different time periods (for 1, 7, 60, and 180 days). Nonpreserved fresh AM was used as a control. An enzyme-linked immunosorbent assay was performed on the supernatant for detection of the following cytokines: epidermal growth factor, basic fibroblast growth factor, hepatocyte growth factor, keratinocyte growth factor, transforming growth factor-beta, and interleukins 4 and 10, and the findings were assessed by post hoc analysis of variance.AM preserved at -80°C showed less decrease in the concentration of 4 cytokines. Three cytokines showed less decrease in AM preserved in the TC199 medium, whereas 1 showed less decrease in AM preserved in dimethyl sulfoxide. After storage, 5 cytokine concentrations remained stable for up to 1 day, 3 remained stable for up to 7 days, and all showed significant loss thereafter.The AM storage temperature of -80°C was found optimal for maintaining the concentrations of most of the tested cytokines, and enriched TC199 medium was the optimal long-term storage medium for maintaining the concentration of 3 of the cytokines, and with less decrease. When possible, AM should be used within 1 to 7 days after harvesting.

HSP90B1 is a gene that codifies heat shock protein 108 (HSP108) that belongs to a group of proteins induced under stress situation, and it has close relation with the nervous system, especially in the retina. Toxoplasma gondii causes ocular toxoplasmosis that has been associated with a late manifestation of the congenital toxoplasmosis although experimental models show that morphological alterations are already present during embryological development. Here, we used 18 eyes of Gallus domesticus embryos in 7th and 20th embryonic days to establish a model of congenital ocular toxoplasmosis, experimentally infected in its fifth day correlating with HSP90B1 gene expression. Embryos' eyes were histologically evaluated, and gene expression was performed by real-time polymerase chain reaction (PCR). Our data showed parasite present in the choroid, unusual migration of retinal pigment epithelium, and chorioretinal scars, and a tendency to a lower expression of the HSP90B1 gene upon experimental infection. This is a promising model to better understand T. gondii etiopathogeny.

Purpose To evaluate the impact of instillation angle and nozzle tip geometry on cross-contamination risk of multidose ocular solution bottles. Methods Pseudomonas aeruginosa solution was passed exclusively on the outside of the nozzle to simulate contamination on the exterior of topical agents. Three drops were administered from angles of 90° and 45° from bottles with either a round or sharp tip geometry, and the cultures were examined for growth. Two-hundred sixteen cultures from nine lubricant eyedrop brands currently existing in the Brazilian market were assessed for bacterial growth. Results After seven days, bacterial contamination was detected in 53.7% of cultures when drops were administered at 90° and in 70.4% of cultures at 45°. Eyedrops collected from a rounded nozzle tip and an instillation angle of 90° transmitted bacteria in 69.4% of cases, whereas those administered from a sharp tip transmitted bacteria in only 22.2% of cases (P = 0.001). At an instillation angle of 45°, contamination was identified in 83.3% of bottles with a rounded tip geometry and in only eight of 18 bottles (44.4%) from those with a sharp nozzle geometry (P = 0.005). Conclusions Adjusting the instillation angle of eyedrop solutions to 90°, as well as using a nozzle geometry that prevents flow of the solution to the side of the bottle, significantly reduced contamination rates. Translational relevance Standardizing drop bottles and adjusting delivery angle shows promise in reducing contamination rates and may critically impact the quality of care for patients requiring topical therapeutic agents.

The initial published clinical report on riboflavin/ultraviolet A corneal cross-linking (CXL) for treatment of progressive keratoconus dates back to 2003. CXL has since then been widely used outside the United States for treatment of progressive keratoconus and post-laser in situ keratomileusis ectasia. The Food and Drug Administration (FDA) approved Avedro Inc.'s corneal cross-linking system (KXL) for treatment of patients with progressive keratoconus and post-laser in situ keratomileusis ectasia in April 2016. The procedure is not currently approved for stable keratoconus. There are 2 FDA-approved topical ophthalmic solutions for use in CXL. Riboflavin 5'-phosphate in 20% dextran ophthalmic solution 0.146% (Photrexa Viscous) and Riboflavin 5'-phosphate ophthalmic solution 0.146% (Photrexa) are intended for use with the KXL system. Photrexa Viscous is used in all CXL procedures, whereas Photrexa is indicated for use when the corneal stroma is thinner than 400 µm after completion of the Photrexa Viscous induction period. The FDA-approved procedure using the Dresden protocol (UV-A, 3 mW/cm for 30 min) induces cytologic and morphologic changes in the anterior 250 to 300 µm of the corneal stroma. It has been believed that a minimum thickness of 400 μm was necessary to protect the corneal endothelium from potential damage. The CXL procedure using the standard Dresden protocol is established as the gold standard for treatment of progressive keratoconus. CXL treatment is indicated for a list of conditions ranging from corneal ectasia to infectious keratitis. Newer protocols, treatment regimens, and expanded indications will require further refinements, investigations, and long-term studies.

Made available in DSpace on 2018-12-11T17:24:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-07-01 Aims To evaluate galectin-3 (Gal-3), a β-galactoside binding protein, as a possible biomarker in ocular allergy and further investigated the role of endogenous Gal-3 in a murine model of ovalbumin (OVA)-induced allergic conjunctivitis (AC). Methods Conjunctival impression cytology specimens from control and patients with severe vernal keratoconjunctivitis, treated or untreated, were used to evaluate Gal-3 expression by immunocytochemistry. To investigate the mechanism of action of Gal-3, OVA-immunised BALB/c male wild-type (WT) and Gal-3 null (Gal-3 -/-) mice were challenged with eye drops containing OVA on days 14-16 with a subset of animals pretreated with 0.03% tacrolimus (TC) or dexamethasone (Dex). Results Patients with AC and OVA-sensitised WT mice exhibited increased levels of Gal-3 in the conjunctiva compared with control, an effect reverted by the action of Dex and TC therapy. Twenty-four hours after the final OVA challenge, total and anti-OVA IgE levels increased significantly in the blood of OVA-sensitised WT and Gal-3 -/- mice compared with controls, supporting the efficacy of the AC model. The lack of endogenous Gal-3 exacerbated the local inflammatory response, increasing the influx of eosinophils and mast cell activation. Additionally, OVA-sensitised Gal-3 -/- animals exhibited increased CD4 + expression in the eyes as well as eotaxin, IL-4, IL-13 and interferon-3 levels in the tear fluid compared with WT animals. Conclusion Gal-3 contributes to the pathogenesis of ocular allergy and represents a relevant therapeutic target. Departamento de Morfologia e Genética UNIFESP - Universidade Federal de São Paulo Programa de Pós-Graduação em Biociências Instituto de Biociências Letras e Ciências Exatas UNESP - Universidade Estadual Paulista Departamento de Oftalmologia e Ciências Visuais UNIFESP - Universidade Federal de São Paulo Departamento de Radiologia e Oncologia FMUSP - Faculdade de Medicina Universidade de São Paulo Instituto Do Câncer Do Estado de São Paulo Programa de Pós-Graduação em Biociências Instituto de Biociências Letras e Ciências Exatas UNESP - Universidade Estadual Paulista

Purpose: This study aimed to determine the variation in diameters of outer and inner apertures of eyedropper tips using a computer vision system. Standardizing the size of eye drop nozzles is crucial to reduce the treatment cost of chronic eye diseases and to ensure a continued use of medication. An eyedropper volume of >20 µL (maximum storage of the conjunctival sac) causes medication wastage and increases treatment costs. Methods: We measured the diameters of the outer and inner apertures of eyedropper tips and evaluated variations in diameters using a computerized visual inspection system. Results: The computer visual inspection system identified anomalies in the apertures of eyedropper tips that resulted in diameter variations. Conclusions: The results of the present study show discrepancies in diameters of eyedropper tips, suggesting a variation in eyedropper size and medication wastage.

Background. Dry eye disease (DED) is one of the most common complications following refractive surgery.Purpose. Evaluate the efficacy of an osmoprotective eye drop (Optive®) for the management of induced DED in refractive surgery patients.Design. Double-masked randomised controlled trial.Methods. Twenty-two refractive surgery patients oriented to apply FreshTears (FT;n=13) or Optive (Op;n=9), topically, QID, for 3 months. Eye exams were performed before surgery (T0) and 1-month (T1) and 3-month (T3) follow-up and consisted of tear film osmolarity, Schirmer 1 test, tear film breakup time (TBUT), fluorescein staining, and ocular surface disease index (OSDI) and patient symptoms questionnaires.Main Outcome Measures. Pain and osmolarity.Results. Pain increased significantly for FT at T3 (p<0.05). A reduction in osmolarity was observed at T1 and T3 for Op group (p<0.01) and at T3 for FT group (p<0.05). TBUT showed a decrease between T0 and T1 for FT (p<0.05). Schirmer 1 values increased significantly for Op in T1.Conclusions. Op was superior to FT in regard to pain, osmolarity, TBUT, and Schirmer 1. Osmoprotectant solutes, such as L-carnitine, could attenuate inflammation and secondary DED. Osmoprotective lubricants can be effectively applied for the prevention of refractive surgery-related dry eye symptoms and signs.

We report intraoperative finding of Granular Corneal Dystrophy Type-1 (GCD1) deposits after stromal pneumodissection in deep anterior lamellar keratoplasty (DALK) in a 61-year-old female. Pneumodissection was performed from the center to the periphery of the cornea, characterizing a big bubble type 1 technique which dissects the deep stroma from the predescemetic layer. After stromal removal, persistence of whitish deposits inside the predescemetic layer was noted. During post-operative evaluation, anterior biomicroscopy and anterior segment optical coherence tomography showed granular opacities between the patient's Descemet's membrane and the donor cornea, suggesting possible involvement of the predescemetic layer in GCD1. This may require the surgeon's attention to choose between DALK keratoplasty or penetrating keratoplasty.

Objective: To determine the mean drop volume produced by artificial tear solutions in different inclination angles and to determine the mean cost of the treatment. Methods: The drop volume of 3 original bottles of the artificial tear solutions Artelac®, Hylo Comod®, Lacrima® Plus, Systane® UL, Lacrifilm®, Hyabak®, Lacribell®, Ecofilm®, Mirugell®, Plenigell®, Fresh Tears®, Optive® and Endura® were determined at the inclination of 90o and 45o. The mean number of drops in each bottle was determined and a pharmacoeconomic evaluation of the drops was made. Results: The drop volume ranged from 32.2 to 64.0 µL at 45o and from 29.1 to 65.1 µL at 90o. The difference between drops in each inclination varied from 2 to 24%. The annual cost was from R$2,73 to R$130,73 according to the inclination of the bottle. The Maximum Duration of Treatment (MDT) was from 29.3 to 51.4 days at 45o and from 28.8 to 48.4 days at 90o, being the difference in MDT from 0.5 to 8 more or less days depending on each brand. Conclusion: None of the collyria studied presented ideal drops for human eyes, leading to a waste of the product and higher cost for the manufacturer and the consumer. We noted that there is a significant variation in the drop volume according to the inclination of the bottle, and that a variation of over 10% would bring financial impact for the patient.

Impression cytology (IC) has been widely used as a method for evaluating the ocular surface and superficial cells layers in the diagnosis and follow-up after treatment of several ocular surface tumors of both epithelial and melanocytic origin. Information regarding this can be found in the English-language literature since 1992. Using either cellulose acetate or Biopore membranes for specimen collection, a high correlation has been found between IC and tissue histology. Compared with exfoliative cytology with spatula, IC is less traumatic to the patient's eye, provides a precise location of the area being studied, and allows accurate observation of the cells the way they exist in vivo. The additional advantage of IC is the preservation of limbal stem cells responsible for continuous corneal epithelium renewal; these can be affected after incisional or excisional biopsy at the corneoscleral limbus, which is the most frequent site of appearance of tumors in the stratified epithelium. Treatment for ocular surface squamous neoplasia has historically included surgery, but nonsurgical interventions have also been adopted. Hence, in certain cases, ophthalmologists may prefer interventions less invasive than surgical biopsy such as of impression cytology for both initial diagnosis and therapeutic monitoring of treatment for ocular surface lesions. Nevertheless, it should be considered that IC may be less helpful if the results conflict with the clinical picture or if the clinical diagnosis is uncertain and results are negative. In such cases, surgical biopsy is required for accurate diagnosis. The purpose of this review is to examine the published literature on the utilization of IC for the diagnosis and management of ocular surface tumors and to discuss the requirement for further investigation on the subject.

Dry eye is a multifactorial disease comprising a wide spectrum of ocular surface alterations and symptoms of discomfort. In most patients with aqueous-deficient dry eye, pharmaceutical tear substitutes are used to control symptoms and prevent ocular surface damage. However, in severe dry eye conditions caused by cicatricial disorders, such as Stevens-Johnson syndrome and ocular cicatricial mucous membrane pemphigoid, noninvasive treatments are insufficient, and patients are at risk of developing complications that can lead to blindness. The use of salivary glands as a source of lubrication to treat severe cases of dry eye has been proposed by different authors. The first reports proposed parotid or submandibular gland duct transplantation into the conjunctival fornix. However, complications limited the functional outcomes. Minor salivary gland autotransplantation together with labial mucosa has been used as a complex graft to the conjunctival fornix in severe dry eye with a good outcome. Our group demonstrated significant improvements in best-corrected visual acuity, Schirmer I test score, corneal transparency, and neovascularization after using this technique. A symptoms questionnaire applied to these patients revealed improvements in foreign body sensation, photophobia, and pain. Similar to tears, saliva has a complex final composition comprising electrolytes, immunoglobulins, proteins, enzymes, and mucins. We demonstrated the viability of minor salivary glands transplanted into the fornix of patients with dry eye by performing immunohistochemistry on graft biopsies with antibodies against lactoferrin, lysozyme, MUC1, and MUC16. The findings revealed the presence of functional salivary gland units, indicating local production of proteins, enzymes, and mucins.