Publications by authors named "José Alvaro P Gomes"

14 Publications

  • Page 1 of 1

Individualized Corneal Cross-linking With Riboflavin and UV-A in Ultrathin Corneas: The Sub400 Protocol.

Am J Ophthalmol 2021 Jan 30;224:133-142. Epub 2021 Jan 30.

Laboratory for Ocular Cell Biology, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland; Department of Ophthalmology, ELZA Institute, Dietikon, Switzerland; Department of Ophthalmology, Paulista School of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil; Faculty of Medicine, University of Geneva, Geneva, Switzerland.

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/cm 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 K (r = -0.215, P = .189). On average, there was a significant change (P < .05) in thinnest stromal thickness (-14.5 ± 21.7 μm), K (-2.06 ± 3.66 D) and densitometry (+2.00 ± 2.07 GSU). No significant changes were found in CDVA (P = .611), sphere (P = .077), or cylinder (P = .915).

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.
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http://dx.doi.org/10.1016/j.ajo.2020.12.011DOI Listing
January 2021

Ocular Surface Microbiome in Health and Disease.

Asia Pac J Ophthalmol (Phila) 2020 Dec;9(6):505-511

Department of Ophthalmology and Visual Sciences, Federal University of Sao Paulo, UNIFESP, Brazil.

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.
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http://dx.doi.org/10.1097/APO.0000000000000330DOI Listing
December 2020

Contribution of Bowman's layer to corneal biomechanics.

J Cataract Refract Surg 2020 Dec 9. Epub 2020 Dec 9.

Computer Vision Laboratory, Swiss Federal Institute of Technology, Zurich, Switzerland.

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.
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http://dx.doi.org/10.1097/j.jcrs.0000000000000543DOI Listing
December 2020

Assessment of the mechanical forces applied during eye rubbing.

BMC Ophthalmol 2020 Jul 22;20(1):301. Epub 2020 Jul 22.

Laboratory for Ocular Cell Biology, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland.

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 < 0,001 and 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.
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http://dx.doi.org/10.1186/s12886-020-01551-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374951PMC
July 2020

TFOS DEWS II iatrogenic report.

Ocul Surf 2017 07 20;15(3):511-538. Epub 2017 Jul 20.

Aston University, Birmingham, UK.

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.
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http://dx.doi.org/10.1016/j.jtos.2017.05.004DOI Listing
July 2017

Human Leukocyte Antigen Class I Genes Associated With Stevens-Johnson Syndrome and Severe Ocular Complications Following Use of Cold Medicine in a Brazilian Population.

JAMA Ophthalmol 2017 04;135(4):355-360

Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto, Prefectural University of Medicine, Kyoto, Japan.

Importance: Describing the association with human leukocyte antigen (HLA) alleles could facilitate the understanding of increased risk factors for development of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients with severe ocular complications (SOCs).

Objective: To investigate the association between HLA class I genes and cold medicine (CM)-associated SJS/TEN with SOCs.

Design, Setting, And Participants: This case-control study was conducted between February 8, 2013, and August 29, 2014. Thirty-nine Brazilian patients with CM-SJS/TEN of 74 patients with SJS/TEN with SOCs and 133 healthy Brazilian volunteers were enrolled. Human leukocyte antigen class I genes (HLA-A, HLA-B, and HLA-C) were examined to determine whether there was a genetic predisposition for CM-SJS/TEN with SOC. Patients were interviewed to identify possible etiologic factors. Data analysis was performed from April 14, 2013, to August 29, 2014.

Main Outcomes And Measures: Genetic predisposition for CM-SJS/TEN with SOCs by analysis of HLA class I genes.

Results: Of 74 patients included in the analysis, 32 (43%) were male; mean (SD) age was 36.01 [15.42] years. HLA-A*66:01 (odds ratio [OR], 24.0; 95% CI, 2.79-206.0; P < .001), HLA-B*44:03 (OR, 2.71; 95% CI, 1.11-6.65; P = .04), and HLA-C*12:03 (OR, 5.6; 95% CI, 1.67-18.80; P = .006) were associated with Brazilian CM-SJS/TEN with SOCs, and HLA-A*11:01 (OR, 0.074; 95% CI, 0.004-1.26; P = .008), HLA-B*08:01 (OR, 0.15; 95% CI, 0.02-1.15; P = .048), and HLA-B*51:01 (OR, 0.23; 95% CI, 0.05-1.03; P = .045) were inversely associated with Brazilian CM-SJS/TEN with SOCs (39 cases: 19 Pardo and 16 European ancestry; 14 males and 25 females; age, 35.2 [14.4] years; and 133 controls: 66 Pardo and 61 European ancestry; 55 males and 78 females; age, 41.2 [12.9] years). When multiple test correction within the HLA locus, HLA-A*66:01 and HLA-C*12:03 demonstrated associations. When participants were segregated into Pardo and locus is considered, HLA-A*66:01 was associated with CM-SJS/TEN with SOC among individuals of both ethnic groups (Pardo: OR, 12.2; 95% CI, 1.19-125.0; P = .03; and European: OR, 21.2; 95% CI, 0.97-465.0; P = .04). An association was observed only in the European cohort for HLA-B*44:03 (OR, 5.50; 95% CI, 1.47-20.50; P = .01) and HLA-C*12:03 (OR, 8.79; 95% CI, 1.83-42.20; P = .008).

Conclusions And Relevance: This study suggests that HLA-A*66:01 might be a marker for CM-SJS/TEN with SOCs in Brazilian individuals of Pardo and European ancestry and that HLA-B*44:03 and HLA-C*12:03 might be markers only in those of European ancestry. Moreover, HLA-A*11:01 might be a marker of resistance to CM-SJS/TEN with SOCs.
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http://dx.doi.org/10.1001/jamaophthalmol.2017.0074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470496PMC
April 2017

The effects of riboflavin and ultraviolet light on keratocytes cultured in vitro.

Arq Bras Oftalmol 2016 May-Jun;79(3):180-5

Ocular Surface Advanced Center (CASO), Department of Ophthalmology and Visual Sciences, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.

Purpose: To culture quiescent human keratocytes and evaluate the effects of ultraviolet light and riboflavin on human corneal keratocytes in vitro.

Methods: Keratocytes were obtained from remaining corneoscleral ring donor corneas previously used in corneal transplant surgeries and cultured in DMEM/F12 with 2% FBS until confluence. Characterization of cultured cells was performed by immunofluorescence analysis for anti-cytokeratin-3, anti-Thy-1, anti-α-smooth muscle actin, and anti-lumican. Immunofluorescence was performed before and after treatment of cultured cells with either ultraviolet light or riboflavin. Corneal stromal cells were covered with collagen (200 µL or 500 µL) and 0.1% riboflavin, and then exposed to ultraviolet light at 370 nm for 30 minutes. After 24 hours, cytotoxicity was determined using MTT colorimetric assays, whereas cell viability was assessed using Hoechst 33342 and propidium iodide.

Results: Cell cultures achieved confluence in approximately 20 days. Expression of the lumican was high, whereas no expression of CK3, Thy-1, and α-SMA was observed. After crosslinking, MTT colorimetric assays demonstrated a low toxicity rate, whereas Hoechst 33342/propidium iodide staining demonstrated a low rate of apoptosis and necrosis, respectively, in all collagen-treatment groups.

Conclusion: Keratocytes can be successfully cultured in vitro and characterized by immunofluorescence using lumican. MTT colorimetric assays, and Hoechst 33342, and propidium iodide staining demonstrated a higher rate of cell death in cells cultured without collagen, indicating collagen protects keratocytes from the cytotoxic effects of ultraviolet light.
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http://dx.doi.org/10.5935/0004-2749.20160052DOI Listing
April 2017

Toxoplasma Gondii Infection of Chicken Embryos Causes Retinal Changes and Modulates HSP90B1 Gene Expression: A Promising Ocular Toxoplasmosis Model.

Eur J Microbiol Immunol (Bp) 2015 Dec 12;5(4):316-20. Epub 2015 Nov 12.

Universidade Federal de São Paulo , Morphology and Genetics Department, Botucatu St., 740, São Paulo, SP, Brazil.

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.
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http://dx.doi.org/10.1556/1886.2015.00024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681359PMC
December 2015

Lamellar keratoplasty in rabbits using human and rabbit amniotic membrane grafts: a comparative study.

Vet Ophthalmol 2015 May 28;18(3):191-7. Epub 2013 Oct 28.

Laboratory of Investigation on Comparative Ophthalmology, School of Veterinary Medicine, University of São Paulo, São Paulo, SP, CEP 02478-000, Brazil.

Objective: To compare the behavior of human and rabbit amniotic membrane (AM) grafts in surgically induced corneal thinning in rabbits.

Animals Studied: Thirty two NZWR were randomly assigned to two groups of 16 animals each according to AM type (Human AM: group HAM and Rabbit AM: group RAM).

Procedure: All animals were submitted to right keratectomy at a depth of 0.1 mm using a 5 mm trephine. Animals from HAM group had a button of 5 mm of human AM sutured into the corneal bed with a continuous pattern and 10.0 nylon monofilament suture, while animals from the RAM group had a button of 6 mm diameter of rabbit AM. Four animals in each group were euthanized 2, 7, 15, and 30 days postoperatively. Their corneas were harvested, fixed in 2% glutaraldehyde solution, and stained with haematoxylin-eosin, picrosirius red, and alcian blue for evaluation under light optical microscopy. Microscope images were digitalized and inflammatory cells and stromal blood vessels were counted.

Results: There were no clinically significant differences between groups, and complete corneal epithelialization was observed in all animals in 30 days. Light optical microscopy revealed AM incorporation and resorption in both groups. However, the number of inflammatory cells and blood vessels was significantly higher in group HAM than in group RAM (P < 0.05, Mann-Whitney test). Clinical responses to human or rabbit AM were similar; however, human AM induced greater inflammatory reaction and stromal neovascularization in the rabbit cornea than in rabbit AM.

Conclusion: These differences may reflect a potential reaction to the xenograft. More studies are needed to further characterize these findings.
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http://dx.doi.org/10.1111/vop.12109DOI Listing
May 2015

Intrastromal injection of bevacizumab in patients with corneal neovascularization.

Arq Bras Oftalmol 2012 Jul-Aug;75(4):277-9

Vision Institute, Department of Ophthalmology, Universidade Federal de São Paulo - UNIFESP - São Paulo (SP), Brazil.

Corneal neovascularization (NV) not only reduces visual acuity, but it also causes loss of the cornea's immune privilege, strongly contributing to a worse prognosis in penetrating keratoplasty. Several mediators participate in corneal angiogenesis, and the role of vascular endothelial growth factor (VEGF) has been extensively proven. Anti-VEGF agents have been shown to be effective in slowing the growth of corneal neovessels. Bevacizumab, an anti-VEGF agent, has been successfully used in the treatment of corneal neovascularization. In this paper, we report a series of patients who underwent intracorneal bevacizumab injections to treat corneal vascularization.
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http://dx.doi.org/10.1590/s0004-27492012000400012DOI Listing
September 2013

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

Cornea 2012 Feb;31(2):181-7

Department of Ophthalmology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

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.
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http://dx.doi.org/10.1097/ICO.0b013e318221ce99DOI Listing
February 2012

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

Br J Ophthalmol 2012 Feb 27;96(2):234-9. Epub 2011 Apr 27.

Alameda dos Quinimuras, 34, Planalto Paulista, São Paulo 04068-000, Brazil.

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 (χ(2) 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 (χ(2) 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.
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http://dx.doi.org/10.1136/bjo.2010.199901DOI Listing
February 2012

Anterior stromal puncture in Brown-McLean syndrome.

J Cataract Refract Surg 2004 Jul;30(7):1575-7

Department of Ophthalmology, Federal University of São Paulo, Rua Botucatu 822, V. Clementino, São Paulo, Brazil CEP 04023-062.

We describe 2 cases of Brown-McLean syndrome with corneal edema successfully treated by anterior stromal puncture (ASP). Ophthalmologic examinations showed peripheral edema and aphakia in both patients. The patients had ASP to control the severe foreign-body sensation. The procedure was effective over a long-term follow-up, suggesting that peripheral ASP may be an effective therapeutic option for patients with symptomatic Brown-McLean syndrome.
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http://dx.doi.org/10.1016/j.jcrs.2003.09.068DOI Listing
July 2004