Prescription trends for preservative free glaucoma medication in a public health system.

PURPOSE: To analyze the prescribing trends over a 7-years period, between 2013 and 2020, in a tertiary hospital (Hospital Clinico San Carlos, Madrid, Spain) and its health area. MATERIAL AND METHODS: A retrospective study on the data collected from the information systems, "farm@web" and "Farmadrid", of glaucoma prescriptions in the framework of a public health system (Spanish National Health System) during the last seven years. RESULTS: Prostaglandin analogues were the most commonly used drugs in monotherapy during the study period (range: 36.82% - 47.07%). Fixed combinations of topical hypotensives had an upward trend since 2013 (range: 39.99% - 54.21%), becoming the most dispensed drugs in 2020 (48.99%). Preservative-free eye drops (lacking benzalkonium chloride, BAK) have displaced preservative containing topical treatments in all pharmacological groups. In 2013, BAK-preserved eye drops accounted for 91.1% of the total prescriptions, however in 2020 they only accounted for 34.2% of total prescriptions. CONCLUSIONS: The results of the present study highlight the current trend to avoid BAK-preserved eye drops for the treatment of glaucoma.

Clinical and multimodal imaging findings in a case of serous maculopathy with absence of retinal pigment epithelium (SMARPE).

INTRODUCTION: The differential diagnosis for serous SRF can involve diseases with widely different pathogenic mechanisms that can range from vascular ocular diseases to ocular tumours and paraneoplastic syndromes. Recently, van Dijk et al. have described in three patients a new entity which they have called serous maculopathy with an absence of retinal pigment epithelium (SMARPE). We hereby describe a case of this infrequent macular disease and report its characteristic findings on multimodal imaging. CASE DESCRIPTION: We present the case of a 65-year-old hyperopic woman with a three-year history of visual acuity (VA) loss in her left eye. Prior optical coherence tomography (OCT) had revealed the presence of serous subretinal fluid that had shown no response to treatment with intravitreal injections. On swept source OCT angiography scan, no macular alterations in the retinal vascular plexus structure were noted and there was no evidence of choroidal neovascularization. Ultra-widefield fluorescence angiography of the left eye revealed an early hyperfluorescent macular spot corresponding to the area of absent RPE and late fluorescein pooling. On ultra-widefield indocyanine green angiography there were no central or peripheral abnormalities of choroidal vascularization. CONCLUSION: This recently described entity should be considered as a differential diagnosis in persistent serous subretinal fluid. Multimodal imaging helps differentiate SMARPE from its main differential diagnoses, and care should be taken to identify and differentiate it from similar conditions to avoid unnecessary treatment with its possible side effects and complications.

PHOTODYNAMIC THERAPY-INDUCED ACUTE EXUDATIVE MACULOPATHY IN A CASE SERIES OF CIRCUMSCRIBED CHOROIDAL HEMANGIOMA.

PURPOSE: To describe the incidence, features, and clinical outcomes of photodynamic therapy-induced acute exudative maculopathy (PAEM) in circumscribed choroidal hemangioma. METHODS: Prospective series of 10 patients who underwent standard-fluence photodynamic therapy for circumscribed choroidal hemangioma. Best-corrected visual acuity in the Early Treatment Diabetic Retinopathy Score and swept-source optical coherence tomography were performed before PDT and 3 days and 1 month after PDT. Central retinal thickness, circumscribed choroidal hemangioma retinal thickness, and subretinal fluid were measured. Photodynamic therapy-induced acute exudative maculopathy was considered as an increase ≥50 µ m in subretinal fluid or intraretinal fluid or the appearance of fibrin 3 days after photodynamic therapy. RESULTS: Six men and four women were included; median age was 55 years (19-69 years). The incidence rate of PAEM was 7 of 10. Five PAEM patients showed an increase in intraretinal fluid, two in subretinal fluid, and one developed abundant fibrin. Median best-corrected visual acuity at baseline was 57.5 letters (5-76 letters) being stable at 1 month (64 letters; 5-80) ( P = 0.03). Median central retinal thickness increased from 516 µ m (262-1,265 µ m) to 664.5 µ m after 3 days and diminished to 245 µ m after 1 month (156-1,363) ( P ≤ 0.022). In 6 of 7 of PAEM, a complete resolution of the fluid was obtained. CONCLUSION: Photodynamic therapy-induced acute exudative maculopathy was frequent in circumscribed choroidal hemangioma, although a favorable prognosis was observed in most cases.

Hyperplasia of the retinal pigment epithelium secondary to subthreshold laser treatment in chronic central serous chorioretinopathy.

PURPOSE: To assess the development of hyperplasia of the retinal pigment epithelium (HRPE) secondary to subthreshold laser treatment (STL) in chronic central serous chorioretinopathy (CSCR). METHODS: Prospective study including 149 eyes of 146 patients with CSCR with persistent subretinal fluid (SRF) that have undergone STL using the Navilas® device. Visual acuity (VA) optical coherence tomography (OCT) and fundus autofluorescence (FAF) were performed before and after the treatment. The HRPE was identified on OCT as a hyperreflective and dense material at the expense of the RPE that did not exist prior to the treatment. The demographics of the patients as well as the parameters of the STL treatments employed were registered. RESULTS: Seven HRPE cases after STL were identified, observing an incidence of 4.7% (7 out of 149 eyes). The mean age was 52.1 ± 3.6 years, being 6/7 males. The mean number of STL sessions was 1.3 ± 0.5. The mean total fluence applied was 52.2 ± 12.4 J/cm2 (range 35.37 to 76.39 J/cm2), using a duty cycle of 10% in all cases. The HRPE was subfoveal in 6 of the 7 cases. The SRF was resolved in 6 of the 7 patients. The mean VA loss was -14.1 ± 14.3 ETDRS letters. CONCLUSION: The development of HRPE secondary to STL in CSCR is an uncommon but severe adverse effect, probably related to the excessive energy employed. Further studies are warranted to minimize the incidence and to know the predictors of this complication after STL treatment to optimize the parameters that should be used.

Subthreshold Micropulse Laser Acute Exudative Maculopathy in Central Serous Chorioretinopathy.

Photodynamic acute exudative maculopathy is a transient increase in subretinal fluid (SRF) within the first days after treatment in different chorioretinal diseases and tumors. Recently, this entity has attracted much attention. However, no cases of acute exudative maculopathy have been described after subthreshold laser (STL). This report presents the case of a 35-year-old male with chronic central serous chorioretinopathy with an extrafoveal serous retinal pigment epithelium detachment (PED) who underwent STL. One day after treatment, the patient noted an acute decrease in visual acuity and abundant SRF. One month after treatment, both the SRF and PED were spontaneously resolved. [Ophthalmic Surg Lasers Imaging Retina 2023;54:540-542.].

Evaluation of the changes in choroidal macular anastomoses after photodynamic therapy and in the follow-up of central serous chorioretinopathy by en face optical coherence tomography.

PURPOSE: To evaluate the changes in the choroidal macular anastomoses after photodynamic therapy (PDT) and in the follow-up of patients with central serous chorioretinopathy (CSCR) by en face optical coherence tomography (EF-OCT). METHODS: Prospective study using EF-OCT images of patients with chronic CSCR treated by PDT with a minimum follow-up of 12 months and with the presence of at least two prominent anastomoses in the macula. Scans of 6 × 6 mm and 12 × 12 mm were made to assess the changes in choroidal macular anastomoses (defined as a diameter ≥150 µm) crossing the medial raphe. EF-OCT was performed before PDT and 3 days, 3 months and at the end of the follow-up after PDT. RESULTS: The mean follow-up time was 23.6 ± 12.1 months. The mean number of anastomoses was 2.5 ± 1.1 in the baseline examination, being 2.3 ± 1.2 in the final examination, with no differences being observed (p = 0.110). A sub-analysis was performed to assess differences in the evolution of the anastomoses between active chronic CSCR and those in which the subretinal fluid (SRF) had been resolved, with no differences being observed in the number or caliber of anastomoses (p = 0.642 and p = 0.306). A significant decrease in the size of anastomoses was found at the 3-day (p<0.01) and 3-month (p = 0.032) visits, but not at the last follow-up visit (p = 0.156). CONCLUSIONS: There was an early decrease in the size of the major macular choroidal anastomotic vessels after PDT treatment. Long-term studies are required to assess its evolution and its possible role in the etiopathogenesis of this disease.

Comment on Torrellas et al. Effectiveness, Safety and Choroidal Changes of a Fovea-Sparing Technique for the Treatment of Chronic Central Serous Chorioretinopathy with Yellow Subthreshold Laser. J. Clin. Med. 2023, 12, 1127.

Recently, we read with great interest the article by Torrellas et al. [...].

TWO-YEAR CLINICAL OUTCOMES AFTER PHOTODYNAMIC ACUTE EXUDATIVE MACULOPATHY IN PATIENTS WITH CHRONIC CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To analyze the 2-year clinical outcomes after photodynamic therapy-induced acute exudative maculopathy (PAEM) in patients with chronic central serous chorioretinopathy. METHODS: Prospective observational study that included 64 eyes of 64 patients with chronic central serous chorioretinopathy who received half-fluence photodynamic therapy and had a 2-year follow-up. Patients were classified into two groups based on whether they had had PAEM at 3 days after treatment (PAEM+, n = 22; ≥50 µ m) increase in subretinal fluid or not (PAEM-, n = 42). Best-corrected visual acuity and subretinal fluid changes evaluated with optical coherence tomography were registered at 3 days, 1 month, 3 months, 1 year, and 2 years after photodynamic therapy. The number of recurrences, the appearance of outer retinal atrophy, and choroidal neovascularization were analyzed. RESULTS: Best-corrected visual acuity was 75.9 ± 13.6 (20/32) and 82.0 ± 11.0 letters (20/25) at 2 years in the PAEM+ and PAEM- groups, respectively ( P = 0.055). There were no differences in the best-corrected visual acuity change (4.2 ± 7.7 vs. 3.3 ± 7.1 letters; P = 0.654) and the subretinal fluid decrease (-117.3 ± 74.2 vs. -138.5 ± 83.6 µ m; P = 0.323) at 2 years between patients with and without PAEM. No differences in the number of recurrences ( P = 0.267), the appearance of choroidal neovascularization ( P = 0.155), or outer retinal atrophy ( P = 0.273) between both groups were noted. CONCLUSION: Patients with chronic central serous chorioretinopathy with and without PAEM presented similar results at 2 years in best-corrected visual acuity gain, subretinal fluid reduction, and complication rate.

Aqueous Humor Cytokine Profile in Primary Congenital Glaucoma.

BACKGROUND: Cytokine profile in patients with primary open-angle glaucoma (POAG) differs from that in healthy controls. Due to the different pathophysiological mechanisms involved in the genesis of primary congenital glaucoma (PCG) and POAG, it is possible that the cytokine profile could also differ. The main objective of this study was to compare the concentrations of cytokines in the aqueous humor of patients with PCG with those of POAG patients and a control group. METHODS: A cross-sectional study was conducted. Aqueous humor samples were taken from PCG and POAG patients eligible for glaucoma or cataract surgery and from patients undergoing cataract surgery. Twenty-seven cytokines were analyzed using the Human Cytokine 27-Plex Immunoassay Kit (Bio-Rad Laboratories, Hercules, CA, USA). RESULTS: A total of 107 subjects were included: patients with PCG (n = 19), patients with POAG (n = 54), and a control group (CG) of patients undergoing cataract surgery (n = 34). Most cytokines measured in aqueous humor in PCG presented decreased values compared with POAG and controls. A statistically significant difference was observed in IL-1ra, IL-2, IL-5, IL-7, IL-8, IL-10, IL-12, IL-15, IL-17A, Eotaxin, FGF basic, G-CSF, GM-CSF, IFN-γ, MIP-1α, PDGF-bb, MIP-1ß, RANTES, TNF-α, and VEGF. CONCLUSION: PCG patients have a cytokine profile in aqueous humor different from POAG patients and patients without glaucoma, characterized by lower concentrations of multiple cytokines.

Anatomical and functional impact of verteporfin shortage in patients with chronic central serous chorioretinopathy.

BACKGROUND: To describe the functional and anatomical impact that the worldwide shortage of verteporfin has had on patients diagnosed with chronic central serous chorioretinopathy (cCSCR) whose treatment with photodynamic therapy (PDT) had to be delayed. METHODS: Prospective observational study. Patients were divided into two groups based on the time interval since PDT had been indicated: groups 1 and 2, with waiting times of less and more than 9 months respectively. Best corrected visual acuity (BCVA), the maximum height of the subretinal fluid (MSRF) and subfoveal choroidal thickness (SFCT) at the baseline visit and the last visit were compared. RESULTS: 49 eyes of 48 patients with cCSCR were included. The mean waiting time for PDT was 9.0 ±3.8 months. The mean BCVA was 69.0 ±17.1 letters and 68.9 ±16.4 letters for the baseline and last visit respectively, showing no difference (p= 0.958). Although there was no difference in the mean global BCVA, 15 eyes (30.5%) showed a deterioration of ≥5 letters, including 7 eyes (14%) with a decrease of ≥10 letters. Mean MSRF height was 151.4 ±97.2 µm and 98.2 ±83.1 µm for the baseline and last visit respectively (p= 0.005), persisting in 74.5% of the eyes. CONCLUSION: No significant impact was observed in the BCVA in cCSCR due to the shortage of verteporfin. However, one-third of patients had BCVA loss. There was a significant spontaneous decrease in MSRF, but it persisted in the majority of the patients, still susceptible to PDT.

Fuji sign: Prevalence and predictive power to photodynamic therapy in chronic central serous chorioretinopathy.

AIM: To determine the prevalence of Fuji sign in central serous chorioretinopathy (cCSC) patients and its predictive power of good response to photodynamic therapy (PDT). METHODS: Retrospective study, including 135 eyes of 130 patients diagnosed with cCSC treated with PDT between 2017 and 2021. Optical Coherence Tomography (OCT) images from these patients were compiled and analyzed. The presence of the Fuji sign, an anatomical finding recently described as a predictor of spontaneous resolution of the subretinal fluid (SRF) in cCSC, as assessed in basal images and the maximum height of SRF pre- and post-PDT OCT was measured. RESULTS: Mean age was 56.6 years, 69.4% were men and the percentage of partial or complete resolution of the SRF after PDT was 75.55%. Only 8.9% of patients (12/135) had positive Fuji sign at baseline OCT. Among them, 50% (6/12) presented a complete response to the PDT (pre-PDT SRF: 109.00 (29.61) µm), 8.3% (1/12) had a partial resolution of the SRF (127 µm to 66 µm) and 41.6% (5/12) did not respond to PDT (pre-PDT SRF: 71.00 (22.82) µm, post-PDT SRF: 83.60 (36.13) µm). CONCLUSIONS: Fuji sign has a low prevalence in cCSC and its presence is not associated with a good response to PDT.

Face mask use and effects on the ocular surface health: A comprehensive review.

In the COVID-19 period, face masks increased exponentially. Several studies suggest that the rise in ocular discomfort symptoms during the pandemic is mostly part of dry eye disease and that these are due to the effect of face masks, resulting in the newly described term MADE, for "mask-associated dry eye". The most commonly proposed mechanism states that wearing a face mask creates an unnatural upward airflow towards the ocular surface during expiration, although the increased temperature, humidity and levels of carbon dioxide of the exhaled air, stress, increased use of video display terminals, as well as changes in the ocular microbiota may contribute. Evidence supports that the use of face masks causes an increase in dry eye disease symptoms, a decreased tear break-up time, corneal epithelial trauma, periocular temperature changes and inflammatory markers secretion. Given that the use of masks may be frequent in some settings in the near future, it is important to establish its effects and consequences on the ocular surface.

Effect of face mask on topographic corneal parameters in healthy individuals.

PURPOSE: To evaluate whether the use of masks has an effect on the measurement of corneal topographic parameters. METHODS: A study including healthy patients with no previous ocular diseases or surgeries was conducted. Corneal topography was evaluated with an elevation topography Pentacam Scheimpflug. Four measurements were taken: two measurements with face mask and another two measurements after 10 min without wearing the face mask. The following parameters were evaluated: anterior topographic flat meridian (K1), anterior topographic steepest meridian (K2), mean keratometry (Km) and maximum keratometric point (Kmax). RESULTS: Thirty-five eyes of thirty-five healthy individuals were included; with a mean age of 33.5 ± 13.8 years (range 24-66) and 26 (74%) being female. Mean time with face-mask was 3.8 ± 2.2 h (range 1-8). No differences in mean K1, K2, Km and Kmax with and without face-mask were noted (paired t-test, all, p > 0.05). Intraclass correlation coefficients (ICC) were excellent for all four analyzed parameters (ICC > 0.914), although they were lower when measurements with face-mask were considered. CONCLUSIONS: Although tear film alterations with the use of face-mask have been described in the literature, no significant differences can be noted in topographic variables.

Long-Term Consequences of COVID-19 Lockdown in Neovascular AMD Patients in Spain: Structural and Functional Outcomes after 1 Year of Standard Follow-Up and Treatment.

Consequences of the COVID-19 pandemic on medical care have been extensively analyzed. Specifically, in ophthalmology practice, patients suffering age-related macular degeneration (AMD) represent one of the most affected subgroups. After reporting the acute consequences of treatment suspension in neovascular AMD, we have now evaluated these same 242 patients (270 eyes) to assess if prior functional and anatomical situations can be restored after twelve months of regular follow-up and treatment. We compared data from visits before COVID-19 outbreak and the first visit after lockdown with data obtained in subsequent visits, until one year of follow-up was achieved. For each patient, rate of visual loss per year before COVID-19 pandemic, considered "natural history of treated AMD", was calculated. This rate of visual loss significantly increased during the lockdown period and now, after twelve months of regular follow-up, is still higher than before COVID outbreak (3.1 vs. 1.6 ETDRS letters/year, p < 0.01). Percentage of OCT images showing active disease is now lower than before the lockdown period (51% vs. 65.3%, p = 0.0017). Although anatomic deterioration, regarding signs of active disease, can be apparently fully restored, our results suggest that functional consequences of temporary anti-VEGF treatment suspension are not entirely reversible after 12 months of treatment, as BCVA remains lower and visual loss rate is still higher than before the COVID-19 pandemic.

Intense pulsed light-based treatment for the improvement of symptoms in glaucoma patients treated with hypotensive eye drops.

BACKGROUND: Ocular surface disease in glaucoma patients is a significant ocular co-morbidity that can affect 40% to 59% of these patients worldwide. The current study was aimed at evaluating the potential clinical benefit of an intense pulsed light (IPL)-based treatment in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatments. To our knowledge, this is the first series analyzing the therapeutic effect of this treatment option in this type of patients. METHODS: This non-comparative prospective case series study enrolled a total of 30 glaucoma patients ranging in age from 57 to 94 years old and treated with hypotensive eyedrops for years with dry eye symptomatology. All patients received four sessions of IPL treatment using the Optima IPL system (Lumenis, Yokneam, Israel) adjusted to the official optimized Lumenis setting. Changes in symptomatology, corneal staining, conjunctival hyperemia, non-invasive break-up time (NIBUT), tear osmolarity, tear meniscus height (TMH), meiboscore and meibomian gland expressibility was analyzed after treatment. RESULTS: Statistically significant reductions were observed after IPL treatment in the symptomatology scores measured with different questionnaires [ocular surface disease index (OSDI), standard patient evaluation of eye dryness (SPEED) and symptom assessment questionnaire in dry eye (SANDE)] as well as with the visual analogue scale (P < 0.001). Mean change in OSDI was - 15.0 ± 11.3. A significant reduction was found after treatment in the corneal staining score (P < 0.001). A significant reduction was found in tear film meniscus height (P = 0.012), as well as in tear film osmolarity (P = 0.001). A significant reduction was also found in meibomian gland expressibility (P = 0.003), changing the percentage of grade 3 eyes from 44.4% before IPL to 17.2% after treatment. CONCLUSIONS: IPL therapy combined with meibomian gland expression (MGX) seems to be an effective option to improve symptomatology in glaucomatous patients with ocular surface disease due to prolonged hypotensive eyedrop treatments, with an additional improvement in clinical signs, such as tear osmolarity and corneal staining.

Effect of Face Mask on Tear Film Stability in Eyes With Moderate-to-Severe Dry Eye Disease.

PURPOSE: The purpose of this study was to evaluate whether tear film stability worsens with the use of masks in patients with dry eye disease, objectively analyzing the tear film stability using noninvasive tear film breakup time (NITBUT) with and without a face mask. METHODS: A cross-sectional study including patients with moderate or severe dry eye disease was conducted. Tear stability was measured using an Oculus Keratograph 5M (Oculus, Wetzlar, Germany), which records NITBUT, both first and average NITBUT. Two measurements were taken: an initial measurement with a mask and a second measurement after 10 minutes without wearing the face mask. RESULTS: Thirty-one patients were included with a mean age of 57.6 ± 11.7 years (range 31-80) and 30 being female (97%). Mean first NITBUT with face mask was 6.2 ± 3.8 seconds (range 2.0-19.8), which increased to 7.8 ± 5.6 seconds (range 2.3-24.0) without the use of mask (P = 0.029), differences being -1.6 ± 0.7 seconds (CI 95% -3.1075 to -0.1770). Mean average NITBUT with a face mask was 12.3 ± 4.8 seconds (range 4.0-19.4) and increased to 13.8 ± 5 seconds (range 5.5-24.0) without the use of mask (P = 0.006), mean difference being -1.5 ± 0.5 seconds (CI 95% -2.5290 to -0.4458). CONCLUSIONS: Face mask use decreases tear film stability in patients with moderate-to-severe dry eye.

Repeatability of Macular and Optic Nerve Head Measurements by Optical Coherence Tomography Angiography in Healthy Children.

Aims: To evaluate the repeatability of the peripapillary and macular vascular parameters using optical coherence tomography angiography (OCT-A) in healthy children.Materials and methods: Cross-sectional study including 34 eyes of 34 healthy children. After a complete medical examination, two consecutive OCT-A exams were done using AngioPlex Cirrus 5000 (Carl Zeiss Meditec, Dublin, CA, USA) in the same session. The scan area used was 6 × 6 mm for the analysis of the superficial vascular plexus (SVP) in the macula, and 4.5 × 4.5 mm for the peripapillary plexus. To study the repeatability of the measurements, the intraclass correlation coefficient (ICC) and the coefficient of variation (CV) of each pair of exams were calculated.Results: The mean age of the children included was 10.77 ± 2.49 years (range 6 to 15 years). Good and excellent ICCs were obtained for all the parameters considered. Peripapillary vascular parameters showed greater reproducibility than macular ones (global peripapillary perfusion density (pPD): ICC = 0.834 CV = 0.89% vs. whole macular area PD (w-mPD): ICC = 0.697 CV = 3.49%; global peripapillary flux index (FI): ICC = 0.858 CV = 1.28%; whole macular area vascular density (VD): ICC = 0.699 CV = 3.30%). Amongst the macular parameters, the characteristics of the foveal avascular zone (FAZ) were the ones showing higher rates of repeatability (FAZ circularity: ICC = 0.858 CV = 8.83%).Conclusion: OCT-A is a non-invasive, time-efficient technology that may be useful in the evaluation of the retinal and peripapillary vascular network in healthy children. The repeatability of the measures will allow the follow-up and evaluation of any change occurring in the macular or optic nerve perfusion.

Predicción computacional de estructura terciaria de las proteínas humanas Hsp27, αB-cristalina y HspB8 / Computational prediction of tertiary structure of the human proteins Hsp27, αB-crystalline and HspB8 / Predição computacional da estrutura terciária das proteínas humanas Hsp27, αB-cristalina e HspB8

Objetivo. Realizar predicciones computacionales de estructura de las proteínas humanas Hsp27, αB cristalina y HspB8. Materiales y métodos. La predicción de la estructura secundaria se obtuvo mediante un consenso de los programas de predicción secundaria GOR 4, nnPred, Sspro, APSSP2, JPredict, Porter, Prof, SOPMA, HNN y Psi-Pred. Los modelos de estructura terciaria se elaboraron a partir de fragmentos homólogos de proteínas con estructura terciaria conocida que fueron obtenidos por múltiples alineamientos. Empleando la secuencia primaria se obtuvieron perfiles de antigenicidad de las proteínas nativas y fueron analizados los perfiles de hidrofobicidad, polaridad, flexibilidad, accesibilidad tanto de las proteínas nativas como de las mutadas. Resultados. Las predicciones de estructura secundaria y terciaria de las proteínas estudiadas muestran que en los tres casos, más del 65% son regiones en coil, 20-25% en hoja plegada y menos del 10% en alfa hélice. Los análisis de estructura primaria muestran que al menos uno de los perfiles estudiados, en cada mutación está alterado. Conclusiones. Los análisis comparativos de estructura sugieren que las mutaciones afectan la solubilidad de las proteínas mutadas y con ello su función como chaperonas moleculares.

Objective: To make computational predictions of the structure of the human proteins Hsp27, αB-crystalline and HspB8. Materials and methods. The prediction of the secondary structure was obtained by a consensus of the programs for secondary prediction GOR 4, nnPred, Sspro, APSSP2, JPredict, Porter, Prof, SOPMA, HNN and Psi-Pred. The models of tertiary structure were built from fragments homologous to proteins with tertiary known structure that were obtained by multiple alignments. Using the primary sequence we obtained the antigenicity profiles of native proteins and we analyzed the profiles of hydrophobicity, polarity, flexibility and accessibility of both native and mutant proteins. Results. Predictions of the secondary and tertiary structures of the studied proteins show that in the three cases, more than 65% are coil regions, 20-25% are folded sheet and less than 10% are alpha helix. Analyses of the primary structure show that at least one of the studied profiles in every mutation is altered. Conclusions. The comparative analyses of structure suggest that mutations affect the solubility of the mutated proteins and hence affect their function as molecular chaperones.

Objetivo. Realizar predições computacionais da estrutura das proteínas humanas Hsp27, αB-cristalina e HspB8. Materiais e métodos. A predição da estrutura secundária foi obtida através de um consenso dos programas de predição secundária GOR 4, nnPred, Sspro, APSSP2, JPredict, Porter, Prof, SOPMA, HNN e Psi-Pred. Os modelos de estrutura terciária foram desenvolvidos a partir de fragmentos homólogos de proteínas com estrutura terciária conhecida que foram obtidos por alinhamentos múltiplos. Utilizando a seqüência primária foram obtidos perfis de antigenicidade das proteínas nativas e foram analisados os perfis de hidrofobicidade, polaridade, flexibilidade e acessibilidade, tanto da proteína nativa, como das mutantes. Resultados. As predições de estrutura secundária e terciária das proteínas estudadas mostram que nos três casos, mais de 65% são regiões em coil, 20-25% de folha pregueada e inferior a 10% em alfa-hélice. A análise da estrutura primária mostra que pelo menos um dos perfis estudados, em cada mutação está alterado. Conclusões. A análise comparativa da estrutura sugere que as mutações afetam a solubilidade das proteínas mutantes e, assim, sua função como chaperones moleculares.