José Álvaro Pereira Gomes

Amniotic membrane transplantation for partial and total limbal stem cell deficiency secondary to chemical burn.

PURPOSE To evaluate the surgical outcome of preserved amniotic membrane transplantation (AMT) for ocular surface reconstruction in chemical burn with limbal stem cell deficiency. DESIGN Prospective, noncomparative, interventional case series. PARTICIPANTS Twenty eyes of 20 consecutive patients with limbal stem cell deficiency secondary to ocular chemical injury. INTERVENTION AMT with or without adjunctive limbal transplantation using limbal tissue from either the healthy contralateral eye (CLAU) or a living related donor (lr-CLAL). MAIN OUTCOME MEASURES Reconstruction of corneal epithelium (clear appearance without epithelial defect, normal fluorescein permeability and the absence of conjunctiva-derived goblet cells on impression cytology), decrease in corneal vascularization and improvement in visual acuity. RESULTS With a mean follow-up time of 19 months (range, 8-27 months), satisfactory ocular surface reconstruction was obtained in 15 eyes (75%), with reduced inflammation and vascularization of the ocular surface and a mean epithelialization time of 3.3 weeks. Success was observed in all cases of partial limbal stem cell deficiency (PLD) and in 68.75% (11 eyes) of cases of total limbal stem cell deficiency (TLD). Surgical failure was observed in five severe cases (31.25%). A significant visual improvement was observed in all cases after surgery, except for 2 eyes that maintained preoperative visual acuity. CONCLUSIONS AMT seems to be an efficient adjunct for ocular surface reconstruction in chemical burns with PLD. When performed in conjunction with limbal stem cell transplantation, it is also effective in most cases of TLD.

Human immature dental pulp stem cells share key characteristic features with limbal stem cells.

Objectives:  Limbal stem cells (LSC) are self‐renewing, highly proliferative cells in vitro, which express a set of specific markers and in vivo have the capacity to reconstruct the entire corneal epithelium in cases of ocular surface injury. Currently, LSC transplantation is a commonly used procedure in patients with either uni‐ or bilateral total limbal stem cells deficiency (TLSCD). Although LSC transplantation holds great promise for patients, several problems need to be overcome. In order to find an alternative source of cells that can partially substitute LSC in cornea epithelium reconstruction, we aimed at investigating whether human immature dental pulp stem cells (hIDPSC) would present similar key characteristics as LSC and whether they could be used for corneal surface reconstruction in a rabbit TLSCD model.

TFOS DEWS II iatrogenic report

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.

Minor salivary glands and labial mucous membrane graft in the treatment of severe symblepharon and dry eye in patients with Stevens–Johnson syndrome

Objective To evaluate minor salivary glands and labial mucous membrane graft in patients with severe symblepharon and dry eye secondary to Stevens–Johnson syndrome (SJS). Methods A prospective, non-comparative, interventional case series of 19 patients with severe symblepharon and dry eye secondary to SJS who underwent labial mucous membrane and minor salivary glands transplantation. A complete ophthalmic examination including the Schirmer I test was performed prior to and following surgery. All patients had a preoperative Schirmer I test value of zero. Results Nineteen patients with severe symblepharon and dry eye secondary to SJS were included in the study. There was a statistically significant improvement in the best spectacle-corrected visual acuity in eight patients (t test; p=0.0070). Values obtained in the Schirmer I test improved significantly in 14 eyes (73.7%) 6 months following surgery (χ2 test; p=0.0094). A statistically significant increase in tear production (Schirmer I test) was found in eyes that received more than 10 glands per graft compared with eyes that received fewer glands (χ2 test; p=0.0096). Corneal transparency improved significantly in 11 (72.2%) eyes and corneal neovascularisation improved significantly in five eyes (29.4%) (McNemar test; p=0.001 and p=0.0005). The symptoms questionnaire revealed improvement in foreign body sensation in 53.6% of the patients, in photophobia in 50.2% and in pain in 54.8% (Kruskal–Wallis test; p=0.0167). Conclusion Labial mucous membrane and minor salivary glands transplantation were found to constitute a good option for the treatment of severe symblepharon and dry eye secondary to SJS. This may be considered as a step prior to limbal stem cell and corneal transplantation in these patients.

Citologia de impressão da superfície ocular: técnica de exame e de coloração

Purpose: To present an examination technique and to standardize the staining procedure of samples of impression cytology of the ocular surface in a reference service. Methods: 28 samples of impression cytology were obtained from patients with ocular surfaces alterations of the External Eye Diseases Sector in the period of July to November 1999. They were stained and microscopically evaluated in the Ocular Microbiology Laboratory of the Federal University of Sao Paulo. Results: We developed a design of a filter paper with apex, base and lateral opening that promoted its adequate position both in the eye at collection and on the glass microscope slides for fixing and staining procedures. The staining technique that uses periodic acid-Schiff, hematoxilin and Papanicolaou is an easy and economic procedure which stains goblet and epithelial cells. Conclusions: The modified method for staining showed to be ideal for the cytologic evaluation of samples of the impression cytology examination. Impression cytology is a very reliable method to study ocular surface, and has proved to be really simple, a cheaper and more confortable procedure for the patient than invasive biopsies.

IKZF1, a new susceptibility gene for cold medicine–related Stevens-Johnson syndrome/toxic epidermal necrolysis with severe mucosal involvement

BACKGROUND Stevens-Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface, oral cavity, and genitals. These reactions are very rare but are often associated with inciting drugs, infectious agents, or both. OBJECTIVE We sought to identify susceptibility loci for cold medicine-related SJS/TEN (CM-SJS/TEN) with severe mucosal involvement (SMI). METHODS A genome-wide association study was performed in 808 Japanese subjects (117 patients with CM-SJS/TEN with SMI and 691 healthy control subjects), and subsequent replication studies were performed in 204 other Japanese subjects (16 cases and 188 control subjects), 117 Korean subjects (27 cases and 90 control subjects), 76 Indian subjects (20 cases and 56 control subjects), and 174 Brazilian subjects (39 cases and 135 control subjects). RESULTS In addition to the most significant susceptibility region, HLA-A, we identified IKZF1, which encodes Ikaros, as a novel susceptibility gene (meta-analysis, rs4917014 [G vs. T]; odds ratio, 0.5; P = 8.5 × 10(-11)). Furthermore, quantitative ratios of the IKZF1 alternative splicing isoforms Ik1 and Ik2 were significantly associated with rs4917014 genotypes. CONCLUSION We identified IKZF1 as a susceptibility gene for CM-SJS/TEN with SMI not only in Japanese subjects but also in Korean and Indian subjects and showed that the Ik2/Ik1 ratio might be influenced by IKZF1 single nucleotide polymorphisms, which were significantly associated with susceptibility to CM-SJS/TEN with SMI.

Trans-ethnic study confirmed independent associations of HLA-A*02:06 and HLA-B*44:03 with cold medicine-related Stevens-Johnson syndrome with severe ocular surface complications

Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucous membranes. Cold medicines including non-steroidal anti-inflammatory drugs and multi-ingredient cold medications are reported to be important inciting drugs. Recently, we reported that cold medicine related SJS/TEN (CM-SJS/TEN) with severe mucosal involvement including severe ocular surface complications (SOC) is associated with HLA-A*02:06 and HLA-B*44:03 in the Japanese. In this study, to determine whether HLA-B*44:03 is a common risk factor for CM-SJS/TEN with SOC in different ethnic groups we used samples from Indian, Brazilian, and Korean patients with CM-SJS/TEN with SOC, and investigated the association between CM-SJS/TEN with SOC and HLA-B*44:03 and/or HLA-A*02:06. We found that HLA-B*44:03 was significantly associated with CM-SJS/TEN with SOC in the Indian and Brazilian but not the Korean population, and that HLA-A*02:06 might be weakly associated in the Korean- but not the Indian and Brazilian population.

Clinical and histopathological outcomes of subconjunctival triamcinolone injection for the treatment of acute ocular alkali burn in rabbits.

Purpose: To evaluate the efficacy and safety of subconjunctival injection of triamcinolone in the treatment of acute ocular alkali burn in rabbits. Methods: Two groups of 5 rabbits were subjected to alkali burn (1 N NaOH). One group was treated with 1 subconjunctival injection of 0.3 mL of triamcinolone and the other with 1 subconjunctival injection of 0.3 mL of 0.9% saline. The affected corneas were observed for vascularization and opacity approximately 10 minutes after the burn and also after 7, 14, and 21 days. Photographs were taken for observation and statistical analyses. At all time intervals, the corneas were classified according to predetermined scores. Twenty-one days after the treatment, the animals were anesthetized, and their eyes were enucleated and processed for histopathology. Results: Greater vascularization and opacity appeared in the animals that were treated with saline than in those treated with subconjunctival triamcinolone (vascularization: 7 days, P = 0.0107; 14 days, P = 0.0099; and 21 days, P = 0.0088; opacity: 7 days, P = 0.0079; 14 days, P = 0.0112; and 21 days, P = 0.0255). These results were also compatible with the morphological and statistical analyses, which revealed a more intense inflammatory process in the group treated with saline (P = 0.0317). No complications, such as corneal melting, perforation, or infection, were observed. Conclusions: Subconjunctival injection of triamcinolone may be a therapeutic option for the treatment of acute ocular burn because it reduced the corneal inflammatory process, opacity, and vascularization, with no apparent clinical changes in the general state of the animal.

Membrana amniótica nas cirurgias reconstrutivas da superfície ocular nas ceratoconjuntivites cicatriciais

Purpose: Amniotic membrane has been consolidated as an useful adjunct in the treatment of ocular surface disorders. Its use is based on the ability to improve epithelial healing and to decrease inflammatory, angiogenic and cicatricial processes. The purpose of this study was to report the surgical outcome of human amniotic membrane use for surface reconstruction in ocular cicatricial diseases. Methods: Amniotic membrane was obtained at the time of cesarean section and was preserved at -80oC in glycerol and cornea culture media at a ratio of 1:1. Eleven eyes of 10 patients underwent amniotic membrane transplantation, associated (8 eyes) or not (3 eyes) with corneal limbal graft. Ocular surface reconstruction was performed after chemical burns (6 eyes), trauma (1 eye) and Stevens-Johnsons syndrome (SJS) (4 eyes). Results: Mean follow-up time was 5.22 months (range, 2-13 months). One case of SSJ developed early postoperative infection and was excluded from the analysis. Successful ocular surface reconstruction was achieved in 8 eyes (80%). Surgical failure was observed in 2 cases of SJS who presented corneal melting at the time of surgery (20%). Conclusions: This study suggests that amniotic membrane transplantation is an effective alternative for surface reconstruction in stable ocular cicatricial diseases. Larger studies with longer follow-up are necessary to further analyse this procedure.

TFOS DEWS II Report Executive Summary

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.