Exhausted T cells in systemic lupus erythematosus patients in long-standing remission.

The mechanisms that drive systemic lupus erythematosus (SLE) patients to achieve remission are unknown; one possible explanation might be T cell exhaustion. The aim of the present study was to measure CD4+ and CD8+ T cell exhaustion in SLE patients in prolonged remission (PR-SLE) and compared them with patients with active SLE (Act-SLE) and healthy subjects. We included 15 PR-SLE patients, 15 Act-SLE and 29 healthy subjects. T cell exhaustion was determined by flow cytometry according to the expression of programmed cell death 1 (PD)-1, T cell immunoglobulin and mucin 3 (Tim-3), natural killer cell receptor (2B4), eomesodermin (EOMES) and T-box transcription factor TBX21 (T-bet) in CD4+ and CD8+ T cells. Dimensionality reduction using the T-distributed stochastic neighbor-embedding algorithm and clustering analysis was used for the identification of relevant populations. Percentages of CD3+ , CD4+ and CD8+ T cells were similar among groups. We identified five subpopulations of CD8+ and seven of CD4+ cells. The CD4+ T-bet+ CD45RO+ cells identified in the unsupervised analysis were significantly increased in PR-SLE versus Act-SLE [median = 0·20, interquartile range (IQR) = 1·74-30·50 versus 1·68, IQR = 0·4-2·83; P < 0·01]. CD4+ EOMES+ cells were also increased in PR-SLE versus Act-SLE (5·24, IQR = 3·38-14·70 versus 1·39, IQR = 0·48-2·87; P < 0·001). CD8+ EOMES+ cells were increased in PR-SLE versus Act-SLE (37·6, IQR = 24·9-53·2 versus 8·13, IQR = 2·33-20·5; P < 0·001). Exhausted and activated T cells presented an increased frequency of PD-1, CD57 and EOMES in SLE patients versus healthy subjects. Some subpopulations of T cells expressing markers associated with exhaustion are increased in patients in remission, supporting T cell exhaustion as a tolerance mechanism in SLE. Exhaustion of specific populations of T cells might represent a potential therapeutic tool that will contribute to the goal of achieving sustained remission in these patients.

Pneumonia in patients with systemic lupus erythematosus: Epidemiology, microbiology and outcomes.

Background and objective Pneumonia remains the main cause of mortality in patients with systemic lupus erythematosus (SLE). The aim of the study was to establish the clinical characteristics, microbiology and risk factors for poor prognosis in patients with SLE and pneumonia. Methods We reviewed medical records of patients with SLE (American College of Rheumatology criteria) and pneumonia who attended the emergency room in a single tertiary care center (January 2010-March 2015). We collected demographics, treatment and disease activity (SLEDAI-2K) data. Severity scales of pneumonia (CURB-65 (acronym for risk factors measured: confusion, urea nitrogen, respiratory rate, blood pressure, 65 years of age and older) and Pneumonia Severity Index (PSI)) were obtained. A negative composite outcome was defined as need for mechanical ventilation, septic shock or death secondary to pneumonia up to 30 days after discharge. We conducted a univariate and multivariable analysis. Results We studied 158 patients (76% women) with 187 episodes of pneumonia. There were no differences in age, SLE duration, SLE activity, treatment or comorbidities between patients with negative composite outcome vs the other group. In 53 episodes, patients presented with a negative composite outcome. Of these, 46 (24.6%) required intubation, 13 (7%) developed shock and 12 (6.4%) died. The most common bacteria isolated was S. aureus, and we observed a high percentage of nonhabitual microorganisms. Fifteen percent of patients who presented with a negative outcome had low values on CURB-65 and PSI scales. Conclusion Patients with SLE and pneumonia have a high risk of complications and present with a high percentage of nonhabitual microorganisms. Severity scales for pneumonia can misclassify as low risk SLE patients with poor prognosis.

Myelitis in systemic lupus erythematosus: clinical characteristics and effect in accrual damage. A single-center experience.

Objective The purpose of this study was to describe the clinical characteristics of acute transverse myelitis, including the time of their presentation, and to evaluate their effect on accrual damage in patients with systemic lupus erythematosus (SLE). Methods Patients with SLE who were hospitalized because of incident, noninfectious myelitis at our institute between January 1997 and December 2013 were identified. As a control group, we selected for each of the patients in the study group one SLE patient hospitalized at the closest date to the case due to other severe non-neuropsychiatric (NP) SLE manifestation, with no history of NP manifestations or noninfectious disease. Clinical characteristics, laboratory results, treatment, disease activity (SLEDAI-2K), and damage (SLICC/ACR-DI) were collected from medical charts at the index hospitalization and one year after hospitalization. Results Demographics and SLE characteristics, including age at SLE diagnosis and time since SLE diagnosis to hospitalization, were comparable in patients with myelitis and controls. At hospitalization, disease activity and cumulative damage were similar in both groups. Patients with myelitis received more aggressive treatment than controls. One year after hospitalization, two of the 15 patients who completed follow-up had symptom improvement without neurologic sequelae, and 13 of them had some improvement of symptoms with neurologic sequelae. Four patients died in the myelitis group, three of them of infectious diseases, and one of alveolar hemorrhage. No patient died because of myelopathy and in the control group no patient died, although three were lost during the follow-up. Disease activity and treatment did not differ between both groups. However, cumulative damage was higher among the patients with myelitis than controls (1.9 ± 0.9 vs 0.75 ± 0.9; p = 0.003). Conclusion Patients with myelitis have clinical characteristics similar to those observed in non-NP SLE and receive more aggressive treatment. Furthermore, myelitis is associated with a significant increase in accrual damage compared with severe non-NP manifestations.

Utility of TWEAK to assess neuropsychiatric disease activity in systemic lupus erhytematosus.

OBJECTIVE: The purpose of this study was to assess the utility of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) in serum and cerebrospinal fluid (CSF) as a biomarker in neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Thirty three NPSLE patients were evaluated at hospitalization and six months later. As controls, five SLE patients with septic meningitis, 51 hospitalized SLE patients without a history of neuropsychiatric (NP) manifestations and without infections, 16 SLE patients without NP manifestations (surgical-SLE), four patients with primary neuropsychiatric disorders, and 25 patients with non-autoimmune diseases were also studied. Serum and CSF samples were drawn at hospitalization, except non-NPSLE patients, in whom only serum was studied, and six months later in 19 NPSLE and 27 non-NPSLE patients. Serum and CSF TWEAK levels were measured by ELISA; values are expressed in pg/mL. RESULTS: The mean ± SD age of NPSLE patients was 31 ± 13.1 years, which was similar across study groups (p = 0.54). TWEAK levels in serum were not different across the study groups. In CSF, TWEAK levels were higher in NPSLE, surgical-SLE and primary neuropsychiatric groups than in non-autoimmune patients: median (IQR) 159.2 (94.1-374.9), 172.3 (125.3-421.9), 371.3 (143-543) vs. 122.1 (76.1-212.4), respectively; all p < 0.05. Six months later, when the neuropsychiatric manifestations were clinically in remission, serum or CSF TWEAK did not vary from baseline in NPSLE patients. CONCLUSIONS: TWEAK levels are slightly elevated in CSF in SLE patients compared with non-autoimmune controls, irrespective of the presence of NP manifestations. TWEAK levels in serum and CSF do not seem to be a useful biomarker of CNS involvement in SLE.

Differential cytokine expression and regulatory cells in patients with primary and secondary Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands. The aim of the study was to characterize and compare the presence of diverse cytokines and regulatory T and B cells in lip minor salivary gland (MSG) biopsies from patients with primary Sjögren's syndrome (pSS), secondary SS (sSS), and patients with connective tissue disease (CTD) without (w/o) SS. We included samples of MSG from 15 pSS, 24 sSS (six scleroderma, nine rheumatoid arthritis and nine lupus patients) and 15 patients with CTD w/o SS. Tissues were examined by an indirect immunoperoxidase technique (goat polyclonal anti-human IL-19, goat polyclonal anti-human IL-22 or mouse monoclonal anti-human IL-24). To determine the subpopulation of CD4(+)/IL-17A(+)-, CD4(+)/IL-4(+)-, CD4(+)/IFN-É£(+)-expressing T cells, CD25(+)/Foxp3(+) Treg cells and CD20(+)/IL-10(+)-producing B cell subset, a double-staining procedure was performed. We estimated the mean percentage of positively staining cells in two fields per sample. CD4(+)/IFN-É£(+), CD4(+)/IL-4(+) and IL-22(+) cell percentages were elevated in both SS varieties; however, the cells were more prevalent in pSS. Patients with pSS had a high number of CD4(+)/IL-17A(+) and IL-19(+) T cells and a lower percentage of IL-24(+) cells (P < 0.05). The Treg and IL-10-producing B cells were increased in pSS (P < 0.05). Concluding, in our patients, a pro-inflammatory and regulatory balance coexists in SS, being both responses more intense in pSS. The explanation of these differences may be related to disease activity, disease duration and treatment.

Identification of novel NOTCH1 mutations: increasing our knowledge of the NOTCH signaling pathway.

BACKGROUND: Alterations in the NOTCH1 signaling pathway are found in about 60% of pediatric T-ALL, but its impact on prognosis remains unclear. PROCEDURE: We extended the previously published CoALL cohort (n = 74) to a larger cohort (n = 127) and additionally included 38 Argentine patients from ALL IC-BFM to potentially identify novel mutations and decipher a stronger discriminatory effect on the genotype/phenotype relationship with regard to early treatment response and long-term outcome. RESULTS: Overall, 101 out of 165 (61.2%) T-ALL samples revealed at least one NOTCH1 mutation, 28 of whom had combined NOTCH1 and FBXW7 mutations. Eight T-ALL samples (4.8%) exclusively revealed FBXW7 mutations. Fifty-six T-ALL (33.9%) exhibited a wild-type configuration of either gene. Four novel NOTCH1 mutations were identified localized in the C-terminal PEST domain, in the rarely affected LNR repeat domain and in the ankyrin domain. Novel LNR mutations may contribute to a better understanding of the structure of the NOTCH1 negative regulatory region (NRR) and the R1946 mutation in the ankyrin domain may represent an unusual loss-of-function mutation. CONCLUSIONS: Overall, NOTCH1 pathway mutations did not affect the relapse rate and outcome of the extended T-ALL cohort uniformly treated according to CoALL protocols, although NOTCH1 mutations were associated with good response to induction therapy (P = 0.009). Individually, HD and PEST domain mutations might exert distinct functional effects on cellular homeostasis under treatment NOTCH1 pathway activity with prognostic implications.

Infiltrating cellular pattern in kidney graft biopsies translates into forkhead box protein 3 up-regulation and p16INK4α senescence protein down-regulation in patients treated with belatacept compared to cyclosporin A.

Renal allograft survival is related directly to cell senescence. In the transplantation scenario many cellular events - participating as immunological and non-immunological factors - could contribute to accelerate this biological process, responsible for the ultimate fate of the graft. Mechanisms concerned in tolerance versus rejection are paramount in this outcome. For this reason, immunosuppressive treatment constitutes an extremely important decision to prevent organ dysfunction and, finally, graft loss. This study was conducted to document the proportion of CD4(+) /interleukin (IL)-17A(+) -, CD16(+) /indoleamine 2, 3-dioxygenase (IDO(+) )-, forkhead box protein P3 (FoxP3(+))-expressing cells, senescent cells (p16(INK) (4α)) and the percentage of interstitial fibrosis (IF) in graft biopsies of kidney transplant recipients participating in the BENEFIT (Bristol-Myers Squibb IM103008) study. CD4(+) /IL-17A(+) , CD16(+) /IDO(+), FoxP3(+) and p16(INK) (4α+) cells were evaluated by immunohistochemistry, and the percentage of IF by morphometry on graft biopsies obtained at time 0 (pre-implantation) and at 12 months post-transplant. Senescent cells and CD4(+) /IL-17A(+) cells were increased among graft biopsies in subjects receiving cyclosporin A (CsA) compared to those under belatacept treatment. Meanwhile, CD16(+) /IDO(+) and FoxP3(+) -expressing cells were lower in biopsies from CsA treatment compared to patients treated with Belatacept. Histological morphometric analyses disclosed more IF in 12-month CsA-treated patients in comparison to pre-implantation biopsy findings. Summing up, renal biopsies from patients receiving belatacept showed greater amounts of FoxP3(+) cells and lower amounts of CD4(+) /IL-17A(+) and senescent cells compared to patients under CsA treatment. Along with these findings, an increase in IF in annual CsA-treated-patients biopsies compared to pre-implantation and belatacept-treated patients were observed.

Subcutaneous administration of polymerized type I collagen downregulates interleukin (IL)-17A, IL-22 and transforming growth factor-ß1 expression, and increases Foxp3-expressing cells in localized scleroderma.

BACKGROUND: Localized scleroderma (LS) is a disfiguring inflammatory autoimmune disease of the skin and underlying tissue. As in systemic sclerosis, a key feature is the presence of T cells in inflammatory lesions. AIM: To evaluate the effect of polymerized type I collagen vs. methylprednisolone (MP) in LS, and to determine the influence of this polymerized collagen (PC) on CD4+ peripheral T cells expressing interleukin (IL)-4, IL-17A, interferon-γ and Forkhead box protein (Foxp)3, and on cells expressing transforming growth factor (TGF)-ß1, IL-17A, IL-22 and Foxp3 in the skin. METHODS: In total, 16 patients with LS were treated for 3 months with monthly subcutaneous intralesional injections of 0.1 mL MP (giving a total dose of 20 mg/mL each month) and 15 patients were treated, with weekly subcutaneous intralesional injections of PC, ranging from 0.2 mL (equivalent to 1.66 mg collagen) for a lesion of 50 mm in size, up to a maximum of 1.0 mL (8.3 mg collagen) for a lesion > 100 mm in size, and followed up for a further 6 months. Skin biopsies were obtained from lesions at baseline (before treatment) and 9 months later (6 months after treatment end). Tissue sections were evaluated by histology and immunohistochemistry (IL-17A, IL-22, TGF-ß1 and Foxp3). CD4+ T-cell subsets were determined in peripheral blood by flow cytometry. RESULTS: Abnormal tissue architecture was seen in the biopsies taken from patients treated with MP, whereas the PC treatment restored normal skin architecture. PC downregulated pro-inflammatory/profibrotic cytokine expression in peripheral cells, and upregulated the number of regulatory T cells (Tregs) in skin. PC was safe and well tolerated. CONCLUSIONS: PC is not only an antifibrotic/fibrolytic agent but also an immunomodulator biodrug that restores the balance between T helper (Th)1, Th2, Th17 and Tregs, downregulates production of pro-inflammatory or profibrogenic cytokines (IL-17A, IL-22 and TGF-ß1), and renews skin architecture, without adverse effects.

[Rehabilitation in Tay-Sachs disease: A case report]. / La rehabilitación en la enfermedad de Tay-Sachs: a propósito de un caso.

Tay-Sachs disease, or GM2 gangliosidosis, is a congenital and neurodegenerative disease caused by the absence or deficiency of the essential enzyme B-hexosaminidase. The timing of the development of neurological manifestations and their severity depend on the mutation, time since disease onset and the patient's characteristics. The disease impairs quality of life and increases mortality. In the most aggressive forms, life expectancy is 3 years. Despite various clinical trials and ongoing research, there is currently no cure for Tay-Sachs disease. Treatment focuses on symptom control and ensuring greater patient wellbeing. Consequently, rehabilitation plays a fundamental role in the management of these patients and in enhancing their quality of life.

Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus.

Interleukin-10 (IL-10) is produced at a high level by B lymphocytes and monocytes of patients with systemic lupus erythematosus (SLE). In the present work, we analyzed whether this increased production of IL-10 contributed to the abnormal production of immunoglobulins (Ig) and of autoantibodies in SLE. The role of IL-10 was compared with that of IL-6, another cytokine suspected to play a role in these abnormalities. The spontaneous in vitro production of IgM, IgG, and IgA by peripheral blood mononuclear cells from SLE patients was weakly increased by recombinant IL (rIL)-6, but strongly by rIL-10. This production was not significantly affected by an anti-IL-6 mAb but was decreased by an anti-IL-10 mAb. We then tested the in vivo effect of these antibodies in severe combined immunodeficiency mice injected with PBMC from SLE patients. The anti-IL-6 mAb did not significantly affect the serum concentration of total human IgG and of anti-double-stranded DNA IgG in the mice. In contrast, the anti-IL-10 mAb strongly inhibited the production of autoantibodies, and, to a lesser extent, that of total human IgG. These results indicate that the Ig production by SLE B lymphocytes is largely IL-10 dependent, and that the increased production of IL-10 by SLE B lymphocytes and monocytes may represent a critical mechanism in the emergence of the autoimmune manifestations of the disease.

Clinical characteristics of systemic lupus erythematosus patients in long-term remission without treatment.

OBJECTIVE: To describe the clinical and serological characteristics of patients with SLE who reached a state of sustained remission for more than 10 years in the absence of treatment. METHODS: From a retrospective cohort of 2121 patients, 44 cases with sustained remission (PtRem) were identified and compared with 88 patients whose course has been chronically active (PtAct).The clinical and serological characteristics were analyzed, as well as the treatment of each group at the beginning of the disease and during its evolution. RESULTS: Older age at disease onset was associated with a tendency to reach a state of prolonged remission. These patients also had a higher frequency of thrombocytopenia at the beginning of the disease 34.1% vs 10.2% (p < 0.001). PtAct had a significantly higher initial SLEDAI compared with cases (10.4 ± 5.6 vs 14.1 ± 5.8; p < 0.001). PtRem had a higher initial frequency of anti-ß2 GP1 IgG antibodies. Also, 25% of these patients were serologically active. We did not find differences in the initial treatment between both groups. The accumulated damage measured by SLICC/ACR damage index at the end of the study was significantly less in the patients who remained in prolonged remission. CONCLUSIONS: Although patients with SLE who achieve prolonged remission have some different characteristics at baseline compared with PtAct, it is not possible to identify a characteristic phenotype for the former. Achieving a state of prolonged remission should always be the goal in patients with SLE. Key Points • SLE patients can reach a very prolonged state of remission, free of treatment, including antimalarials, for at least 10 years. • Venous thromboembolism and thrombocytopenia are commonly present in patients that achieved remission. • The presence of serological markers of activity, even after 10 years in remission, is a risk factor for relapse.

Correction: Clinical characteristics of systemic lupus erythematosus patients in long-term remission without treatment.

The original published version of the above article contained errors in Key Points and Conclusion sections.

Prognostic significance of metabolic tumor volume and total lesion glycolysis in patients with advanced cervical carcinoma. / Significación pronóstica del volumen metabólico tumoral y de la glucólisis tumoral total en pacientes con cáncer cervical avanzado.

AIM: 18-Fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG PET/CT) is considered to be the most accurate image method of detection of node or distant metastases in cervical cancer. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of 18F-FDG PET/CT are volumetric measurements of tumor cells with increased 18F-FDG uptake. The prognostic value of MTV and TLG in patients with advanced cervical cancer (ACC) were evaluated. METHODS: 38 patients with ACC from one tertiary university hospital underwent 18F-FDG PET/CT between June 2009 and December 2015. Clinicopathologic factors and various PET parameters were analyzed to evaluate their relationship with recurrence-free survival (RFS) and overall survival (OS). These parameters were: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUV mean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor, of the pelvic nodes, of the paraaortic nodes and the metabolic volume of the metastases if any. RESULTS: A total of 38 patients with ACC fulfilled the inclusion criteria. All of them underwent a 18F-FDG PET/CT before definitive chemoradiotherapy. In the univariate analyses higher tumor size, pelvic lymph node metastasis and both MTV and TLG showed a significant association with OS and with RFS (MTV HR=1.55, p=0.011 and TLG HR=1.43, p=0.017 for RFS and MTV HR=1.82, p=0.006 and TLG HR=1.67, p=0.007 for OS). CONCLUSION: Pretreatment TLG sum and MTV sum seem to be independent prognostic factors for OS and RFS in patients with advanced cervical cancer treated with definitive chemoradiotherapy and they are better than the classic measurement of SUVmax.

Piezoelectric focal waves application in the treatment of plantar fascitis. / Aplicación de ondas de choque focales piezoeléctricas en el tratamiento de la fascitis plantar.

INTRODUCTION: Plantar fasciitis (PF) is one of the most frequent causes of thalalgia and disability. The effectiveness of extracorporeal shock wave therapy is an ideal alternative to conservative treatments. OBJETIVE: To evaluate the effectiveness of the treatment with Piezoelectric Focal Shock Waves with echographic support and maintenance of the effect at 3 and 6 months. MATERIALS AND METHODS: Causi-experimental, retrospective statistical study,June 2015 to June 2017, of 90 patients, 36.6% men and 63.3% women, with a mean age of 52 years, diagnosed with PF. Three sessions (one weekly for 3 weeks) of shock wave therapy (PiezoWave F10 G4 generator) were performed, with echographic support and weekly revision and at 3 and 6 months. MAIN VARIABLES: pain,using Visual Analog Scale before and after each session and at 3 and 6 months and Roles and Maudsley Scale at the end of treatment and at 3 and 6 months. RESULTS: 2000 pulses per session were applied, medium energy intensity 0.45 mJ /mm2, median frequency 8 MHz and median depth of focus of 15 mm. Statistically significant improvement was observed in the Visual Analog Scale between the 3 treatment sessions and after 3 and 6 months posttreatment,obtaining a statistically significant improvement in all values (p <0.05). CONCLUSION: Treatment with piezoelectric focal shock waves in PF may reduces pain from the first session and achieves a subjective perception of improvement, maintaining these results at 6 months post -treatment.

Histone deacetylase inhibitors: mechanism of action and therapeutic use in cancer.

Histone deacetylases (HDACs) remove the acetyl groups of lysine residues of histone tails leading to chromatin compaction and transcriptional repression. In addition, HDACs can also influence transcription-independent events such as mitosis or deoxyribonucleic acid (DNA) repair and deacetylate nonhistone proteins involved in cell proliferation and death, altering their function. Histone deacetylase inhibitors (HDACi) constitute a promising treatment for cancer therapy due to their low toxicity. HDACi have been shown to induce differentiation, cell-cycle arrest, and apoptosis and to inhibit migration, invasion, and angiogenesis in many cancer cell lines. In addition, these compounds inhibit tumor growth in animal models and show antitumor activity in patients. HDACi alone and in combination with a variety of anticancer drugs are being tested in clinical trials, showing significant anticancer activity both in hematological and solid tumors. SAHA (vorinostat, Zolinza) was the first HDACi approved by the US Food and Drug Administration to enter the clinical oncology market for treating cutaneous T-cell lymphoma (CTCL) and is being tested for other malignancies.

Autologous rosette-forming T cells as the responding cells in human autologous mixed-lymphocyte reaction.

Autologous rosette-forming cells (Tar cells) have surface and functional characteristics of post-thymic precursors and among these characteristics there are some that have been identified in the responsive cell of the autologous mixed-lymphocyte reaction (AMLR). We therefore did AMLR with circulating mononuclear cells from normal subjects using as responding cells either total T cells, T cells depleted of Tar cells, or purified Tar cells. The response of Tar cells in AMLR was significantly greater than that of total T cells and these responded significantly more than Tar-depleted T cells. Conversely, Tar cells responded less than total T cells or T cells depleted of Tar cells in allogeneic mixed-lymphocyte reactions. Increasing numbers of Tar cells gave significantly greater AMLR responses both alone and when added to diminishing proportions of Tar-depleted T cells to keep the number of T cells constant in the system. Tar cells are the responding cells in AMLR but not in allogeneic mixed-lymphocyte reactions.

HLA class II genotypes in Mexican Mestizos with familial and nonfamilial multiple sclerosis.

Predisposition to MS is associated with the HLA-DR2 antigen in white patients. The authors investigated the genetic factors behind the increasing frequency of MS in the Mexican population. HLA-DR and DQ were analyzed in 17 patients with MS, 15 of their first-degree relatives, and 99 healthy ethnically matched controls. DR2 or DR3 was found in 15 of 17 patients. In controls, both alleles had frequencies less than 0.05. MS in Mexican patients was associated with HLA-DR2 and DR3.

Optical response to LASIK surgery for myopia from total and corneal aberration measurements.

PURPOSE: To evaluate the optical aberrations induced by LASIK refractive surgery for myopia on the anterior surface of the cornea and the entire optical system of the eye. METHODS: Total and corneal aberrations were measured in a group of 14 eyes (preoperative myopia ranging from -2.5 to -13 D) before and after LASIK surgery. Total aberrations were measured using a laser ray-tracing technique. Corneal aberrations were obtained from corneal elevation maps measured using a corneal system and custom software. Corneal and total wave aberrations were described as Zernike polynomial expansions. Root-mean-square (RMS) wavefront error was used as a global optical quality metric. RESULTS: Total and corneal aberrations (third-order and higher) showed a statistically significant increase after LASIK myopia surgery, by a factor of 1.92 (total) and 3.72 (corneal), on average. This increase was more pronounced in patients with the highest preoperative myopia. There is a good correlation (r = 0.97, P < 0.0001) between the aberrations induced in the entire optical system and those induced in the anterior corneal surface. However, the anterior corneal spherical aberration increased more than the total spherical aberration, suggesting also a change in the spherical aberration of the posterior corneal surface. Pupil centration and internal optical aberrations, which are not accounted for in corneal topography, play an important role in evaluating individual surgical outcomes. CONCLUSIONS: Because LASIK surgery induces changes in the anterior corneal surface, most changes in the total aberration pattern can be attributed to changes in the anterior corneal aberrations. However, because of individual interactions of the aberrations in the ocular components, a combination of corneal and total aberration measurements is critical to understanding individual outcomes, and by extension, to designing custom ablation algorithms. This comparison also reveals changes in the internal aberrations, consistent with the posterior corneal changes reported using scanning slit corneal topography.

Ocular aberrations before and after myopic corneal refractive surgery: LASIK-induced changes measured with laser ray tracing.

PURPOSE: To determine objectively the changes in the ocular aberrations (3rd order and above) induced by myopic LASIK refractive surgery and its impact on image quality. METHODS: The ocular aberrations of 22 normal myopic eyes (preoperative refraction ranged from -13 to -2 D) were measured before (2.9 +/- 4.3 weeks) and after (7.7 +/- 3.2 weeks) LASIK refractive surgery using a laser ray tracing technique. A set of laser pencils is sequentially delivered onto the eye through different pupil locations. For each ray, the corresponding retinal image is collected on a CCD camera. The displacement of the image centroid with respect to a reference provides direct information of the ocular aberrations. Root-mean-square (RMS) wavefront error was taken as image quality metric. RESULTS: RMS wavefront error increased significantly in all eyes but two after surgery. On average, LASIK induced a significant (P = 0.0003) 1.9-fold increase in the RMS error for a 6.5-mm pupil. The main contribution was due to the increase (fourfold, P < 0.0001) of spherical aberration. The increase in the RMS for a 3-mm pupil (1.7-fold) was also significant (P = 0.02). The modulation transfer (computed for 6.5-mm pupil) decreased on average by a factor of 2 for middle-high spatial frequencies. CONCLUSIONS: (1) Laser ray tracing is a well-suited, robust, and reliable technique for the evaluation of the change of ocular aberrations with refractive surgery. (2) Refractive surgery induces important amounts of 3rd and higher order aberrations. The largest increase occurs for spherical aberration. Decentration of the ablation pattern seems to generate 3rd order aberrations. (3) This result is important for the design of customized ablation algorithms, which should cancel existing preoperative aberrations while avoiding the generation of new aberrations.