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RationaleFactors associated with long-term sequelae emerging after the acute phase of COVID-19 (so called “long COVID”) are unclear. Here, we aimed to identify risk factors for the development of COVID-19 sequelae in a prospective cohort of subjects hospitalized for SARS-CoV-2 infection and followed up one year after discharge.MethodsA total of 324 subjects underwent a comprehensive and multidisciplinary evaluation one year after hospital discharge for COVID-19. A subgroup of 247/324 who consented to donate a blood sample were tested for a panel of circulating cytokines.ResultsIn 122 patients (37.8%) there was evidence of at least one persisting physical symptom. After correcting for comorbidities and COVID-19 severity, the risk of developing long COVID was lower in the 109 subjects admitted to the hospital in the third wave of the pandemic than in the 215 admitted during the first wave, (OR 0.69, 95%CI 0.51-0.93, p=0.01). Univariable analysis revealed female sex, diffusing capacity of the lungs for carbon monoxide (DLCO) value, body mass index, anxiety and depressive symptoms to be positively associated with COVID-19 sequelae at 1 year. Following logistic regression analysis, DLCO was the only independent predictor of residual symptoms (OR 0.98 CI 95% (0.96-0.99), p=0.01). In the subgroup of subjects with normal DLCO (> 80%), for whom residual lung damage was an unlikely explanation for long COVID, the presence of anxiety and depressive symptoms was significantly associated to persistent symptoms, together with increased levels of a set of pro-inflammatory cytokines: interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-12, IL-1β, IL-17. In logistic regression analysis, depressive symptoms (p=0.02, OR 4.57 [1.21-17.21]) and IL-12 levels (p=0.03, OR 1.06 [1.00-1.11]) 1-year after hospital discharge were independently associated with persistence of symptoms.ConclusionsLong COVID appears mainly related to respiratory sequelae, prevalently observed during the first pandemic wave. Among patients with little or no residual lung damage, a cytokine pattern consistent with systemic inflammation is in place.

PURPOSE: To evaluate a new curvature gradient topography map to predict postoperative corneal remodeling. METHODS: In this retrospective study, 32 eyes of 16 patients with myopia underwent excimer ablation surgery with a postoperative high curvature gradient. The new curvature gradient map (acquired immediately postoperatively) shows the difference between the curvatures of two points over the distance between them; it was compared to the tangential curvature difference map between 1 and 12 months postoperatively to determine their relationship. Corneas were divided into 12 regions for analysis: four 90°-wide sectors centered on 0°, 90°, 180°, and 270°. There were three subdivisions in each sector: central (radius: 0 to 2.75 mm), paracentral (radius: 2.75 to 3.25 mm), and peripheral (radius: 3.25 to 4.5 mm). Linear regression analysis was performed by region. RESULTS: The following regions had significant relationships between the initial curvature gradient and curvature difference between 1 and 12 months postoperatively: the paracentral zone of the 90° sector ( P = .0145; R 2 = 0.1832) and both the central ( P = .0034; R 2 = 0.2522) and paracentral ( P = .0452; R 2 = 0.1271) zones of the 270° sector. The greatest average initial tangential curvature was in the 270° sector. CONCLUSIONS: The initial curvature gradient after surgery predicted change in tangential curvature over the subsequent 12 months in areas where initial tangential curvature was greatest. When the curvature gradient was high, the surface curvature modification remained in progress months after surgery. [ J Refract Surg . 2014;30(3):202–207.]

To report refractive, topographic, tomographic, and aberrometric outcomes 12 months after corneal cross-linking (CXL) in eyes with progressive advanced keratoconus.Prospective, nonrandomized, single-center clinical study.Twenty-eight eyes undergoing CXL between April and June 2006.Riboflavin-ultraviolet A (UVA)-induced CXL included instillation of 0.1% riboflavin-20% dextrane solution 30 minutes before UVA irradiation and every 5 minutes for an additional 30 minutes during irradiation.Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), sphere and cylinder refraction, topography, tomography, aberrometry, and endothelial cell count were evaluated at baseline and at 1, 3, 6, and 12 months follow-up.Mean baseline UCVA and BSCVA were 0.17+/-0.09 and 0.52+/-0.17, respectively; 12-month mean UCVA and BSCVA were 0.27+/-0.08 and 0.72+/-0.16, a statistically significant difference (P0.05). Mean spherical equivalent refraction showed a significant decrease of 0.41 diopters (D). Mean baseline simulated keratometry (SIM K) flattest and steepest meridians and SIM K average were 46.10, 50.37, and 48.08 D, respectively; at 12 months, 40.22, 44.21, and 42.01 D, respectively, were recorded, a difference that was significant for all 3 indices (P0.05). Mean average pupillary power (APP) changed significantly from 47.50 to 41.04 D at 12 months (P0.05) and apical keratometry (AK) from 58.94 to 55.18 D (P0.05). The treated eyes showed no deterioration of the Klyce indices at 6 months postoperatively, whereas the untreated (contralateral) eyes did show deterioration. For a 3-mm pupil, there was a significant reduction (P0.05) in whole eye (total), corneal, higher order, and astigmatic wavefront aberrations. A significant difference (P0.05) in total coma and total spherical aberration after CXL was also observed. Mean baseline pupil center pachymetry and total corneal volume decreased significantly (P0.05) to 470.09+/-29.01 microm and 57.17+/-3.21 mm(3) from baseline values of 490.68+/-30.69 microm and 59.37+/-4.36 mm(3), respectively. Endothelial cell counts did not changed significantly (P=0.13).Corneal cross-linking seems to be effective in improving UCVA and BSCVA in eyes with progressive keratoconus by significantly reducing corneal APP, AK, and corneal and total wavefront aberrations at 1 year postoperatively.

• PURPOSE: To evaluate the impact of different definitions of primary open angle glaucoma (POAG) on assessment of the diagnostic validity of Heidelberg Retinal Tomography (HRT). • DESIGN: Retrospective, cross-sectional study. • METHODS: A search of medline (1992-2003) led to the retrieval of 181 papers containing definitions of POAG, including the eight visual field (VF)-based definitions used for this study. A sample of 193 normal subjects, 222 patients with suspected POAG, and 103 with POAG underwent HRT and the 24 II Humphrey VF examinations to assess the diagnostic validity of HRT. POAG was defined on the basis of Glaucoma Hemifield Test (GHT) "out of normal limits" associated with corrected pattern standard deviation (CPSD) > 2 dB and intraocular pressure (IOP)

Purpose: To assess intraobserver and interobserver reproducibility of the measurement of stereometric parameters of the optic disc by means of the Heidelberg Retina Tomograph I (HRT). Study design: Observational study, with interobserver variability. Participants: Fifty-five volunteers (healthy subjects and patients with glaucoma). Methods: HRT examination of the optic disc was repeated on 3 consecutive days on 1 eye of each of the 55 subjects. During each session, five single images were randomly acquired by two independent observers. One mean topography image (MTI), based on three single images, was then built at each session. For the intraobserver intraimage evaluation, the two observers traced their own contour line on one randomly chosen MTI. This procedure was repeated three times. For the intraobserver interimage and interobserver intra/interimage evaluations, the two observers traced their own contour line on the MTI of the first session, which was then automatically superimposed on the MTIs of the other two sessions. Main Outcome Measures: Reproducibility of the 12 stereometric parameters was calculated for each observer by means of the intraclass correlation coefficient (ICC). The expected range of variability between two independent evaluations was calculated by the scatter-plots of each test-retest difference versus their mean. The standard deviation of the mean test-retest score differences was used to describe the spread of score differences. Results: The ICC ranged between 0.79 and 0.99 for intraobserver intraimage and between 0.56 and 1 for intraobserver interimage evaluation. The ICC ranged between 0.54 and 0.99 for interobserver intraimage and between 0.65 and 0.97 for the interobserver interimage evaluation. ICC was almost perfect to perfect for planimetric measures (0.81 < ICC ≤ 1), substantial to almost perfect for volumetric and cup measures (0.61 < ICC ≤ 0.99), and moderate to almost perfect for retinal nerve fiber layer related measures (0.41 < ICC < 0.99). The expected variability was low (95% confidence interval

To report refractive, topographic, aberrometric, and tomographic outcomes 24 months after corneal cross-linking (CXL) in patients up to 18 years of age with progressive keratoconus.Prospective, interventional case series.Forty eyes underwent riboflavin-ultraviolet A-induced CXL. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), sphere and cylinder, topography, aberrometry, tomography, and endothelial cell counts were evaluated at baseline and at 1, 3, 6, 12, and 24 months.Mean logarithm of the minimum angle of resolution baseline UCVA and BSCVA were 0.79 ± 0.21 and 0.39 ± 0.10, respectively. Mean UCVA and BSCVA at 2 years were 0.58 ± 0.18 and 0.20 ± 0.09, respectively. The improvement in UCVA and BSCVA was significant throughout the postoperative follow-up (P.05). Mean spherical equivalent refraction showed a significant decrease of 1.57 diopters (D) at 24 months (P = .02). Mean baseline simulated keratometry was 46.32 D in the flattest meridian and 51.48 D in the steepest meridian; at 2 years, the values were 45.30 D (P = .04) and 50.21 D (P = .07), respectively. For a 3-mm pupil, there was a significant reduction (P.05) in whole eye (total), corneal, higher-order, and astigmatic wavefront aberrations at 24 months. A significant difference (P.05) in total coma and total spherical aberration 2 years after CXL also was observed. Mean baseline pupil center pachymetry decreased significantly (P = .04) at 6 months, but recovered by 12 months and remained stable thereafter through the 2-year follow-up. Endothelial cell counts did not change significantly (P = .32).CXL improved UCVA and BSCVA in the study patients, most likely by significantly reducing corneal asymmetry and corneal as well as total wavefront aberrations.

Objectives: To report intraoperative and 24-month refractive, topographic, tomographic, and aberrometric outcomes after corneal collagen cross-linking in progressive advanced keratoconus. Methods: Prospective, nonrandomized single-center clinical study involving 28 eyes. Main outcome measures included uncorrected and best spectaclecorrected visual acuities, sphere and cylinder refraction, topography, tomography, aberrometry, and endothelial cell count evaluated at baseline and follow-up at 1, 3, 6, 12, and 24 months after treatment. Topography was also recorded intraoperatively. Results: Two years after treatment, mean baseline uncorrected and best spectacle-corrected visual acuities improved significantly (P=.048 and.001, respectively) and mean spherical equivalent refraction decreased significantly (P=.03). Mean baseline flattest and steepest meridians on simulated keratometry, simulated keratometry average, mean average pupillary power, and apical keratometry all decreased significantly (P.03). Deterioration of the Klyce indices was observed in the untreated contralateral eyes but not in treated eyes. Total corneal wavefront aberrations Z0 (piston), Z2 (defocus), and Z7 (III coma) decreased significantly (P.046). Mean 12-month baseline pupil center pachymetry and total corneal volume decreased significantly (P=.045). Endothelial cell counts did not change significantly (P=.13). Conclusions: Two years postoperatively, corneal collagen cross-linking appears to be effective in improving uncorrected and best spectacle-corrected visual acuities in eyes with progressive keratoconus by significantly reducing corneal average pupillary power, apical keratometry, and total corneal wavefront aberrations. Arch Ophthalmol. 2009;127(10):1258-1265

Purpose: To evaluate the 1-year results of corneal collagen cross-linking (CXL) in eyes with postoperative excimer laser refractive surgery corneal ectasia. Methods: Thirteen eyes of 9 consecutive patients who had undergone excimer laser refractive surgery (photorefractive keratectomy [n=3], LASIK [n=10]) with resultant unstable corneal ectasia underwent CXL with photosensitizing riboflavin 0.1% solution and subsequent exposure to ultraviolet radiation. Study eyes underwent complete ophthalmologic examination, endothelial specular microscopy, corneal topography, and aberrometry as well as central pachymetry and Scheimpflug-based topo/tomography preoperatively and at 3-, 6-, and 12-month intervals. Results: Best spectacle-corrected visual acuity (BSCVA) improvement was statistically significant ( P P Conclusions: One year after surgery, CXL appears to stabilize eyes with ectasia consequent to excimer laser refractive surgery and improve BSCVA.

Purpose: To report the outcomes of topography-guided photorefractive keratectomy (PRK) for the treatment of myopia with or without astigmatism using the customized aspheric transition zone (CATz) ablation algorithm. Methods: In this study, 335 eyes underwent PRK using the NIDEK Advanced Vision Excimer laser platform (NAVEX). Mean preoperative manifest refraction spherical equivalent was −4.42±3.46 diopters (D) (range: −14.50 to ±0.50 D). Mean preoperative sphere was −3.94±3.43 D (range: −13.00 to −1.00 D), and mean preoperative cylinder was −0.96±1.05 D (range: −5.50 to 0.00 D). Refractive outcomes out to 1 year postoperatively were analyzed. Results: At least 6 months postoperatively, all eyes maintained or gained lines of best spectacle-corrected visual acuity (BSCVA). There was a 51% increase in the eyes that read 20/16 or better uncorrected compared with preoperative BSCVA. At 1 year postoperative, 252/280 (90%) eyes had BSCVA 20/20 or better. Refractive outcomes within ±0.50 D were observed in 223/275 (81%) eyes at 3 months, 228/300 (76%) eyes at 6 months, and 187/280 (67%) eyes at 1 year. Conclusions: Topography-guided PRK using CATz for the treatment of low, moderate, and high myopia is safe, effective, and predictable. [ J Refract Surg . 2009;25: S89–S92.]

Purpose: To analyze intra- and postoperative variation in Ocular Response Analyzer (ORA, Reichert Ophthalmic Instruments) parameters in 24 keratoconic eyes undergoing corneal cross-linking (CXL). Methods: In a prospective clinical study, corneal hysteresis (CH), corneal resistance factor (CRF), peak 1 and peak 2 amplitude, corneal-compensated and Goldmann-correlated intraocular pressure (IOP) were evaluated using the ORA. The thinnest cornea point was measured with the Pentacam (Oculus Inc). Corneal topography and endothelial cell count were performed. Measurements were recorded at baseline; intraoperatively after epithelium removal, riboflavin impregnation, and ultraviolet A irradiation; and postoperatively after corneal re-epithelialization and at 1, 6, and 12 months. Results: A statistically significant reduction of the thinnest cornea point from 462±23.24 μ m was observed at the end of the CXL procedure intraoperatively and at 1- and 6-month follow-up ( P μ m was found after re-epithelialization ( P P P >.05). Conclusions: The results showed a significant change in ORA parameters and the thinnest cornea point during and after the CXL procedure and a high correlation between peak amplitudes and corneal asymmetry, providing insight to the bioelastic and biomechanical behavior of the cornea during and after CXL.

PURPOSE: To compare the long-term refractive outcomes and changes in higher order wavefront aberrations in patients undergoing photorefractive keratectomy (PRK) with topography-guided (CATz) or wavefront-guided (OPDCAT) ablation algorithm using the NIDEK Advanced Vision Excimer Laser System (NAVEX). METHODS: A retrospective 12 -month follow-up study was conducted of 226 eyes undergoing PRK. The NIDEK EC-5000 CX Il excimer laser and Final Fit 1.11 treatment planning software were used. Sixty-eight eyes underwent OPDCAT ablation and 158 eyes underwent CATz ablation. Mean preoperative manifest refractive spherical equivalent (MRSE) was -5.73±2.03 diopters (D) (range: -11.25 to -2.50 D) in the OPDCAT group and -3.77±3.78 D (range: -12.50 to -5.75 D) in the CATz group. RESULTS: At 12 months postoperatively, mean MRSE was 0.05 D for the OPDCAT group and piano for the CATz group. Stability was similar in both groups as were visual outcomes. No eyes lost 2 or more lines of BSCVA at 6 months postoperatively or later. Mean ocular wavefront higher order aberrations at 3 months postoperatively were 0.44±0.17 µ?? for the OPDCAT group and 0.55±0.27 /im for the CATz group. CONCLUSIONS: Refractive outcomes were equivalent between eyes that underwent PRK with wavefront-guided ablation and those that underwent topography-guided ablation. [J Refract Surg. 2007;23:S1029-S1036.]

Purpose: To describe a new keratoplasty procedure using intraoperative topography to reduce postoperative astigmatism. Methods: One hundred sixty-five eyes of 150 consecutive patients were enrolled in this prospective study. The most common diagnosis was keratoconus (78.8%). As many as 5.5% had post‐laser in situ keratomileusis ectasia. Keratoplasty was performed with the Hanna Corneal Trephine System. A 24-bite running suture was placed, using a specially developed marker. Suture adjustment was performed with the aid of an intraoperative topographer (Keratron Scout; OPTIKON 2000, Rome, Italy). The aim of the adjustment was to obtain an astigmatism #2.0 D on the operating table. In case of .3.0 D of astigmatism at 1 month after surgery, suture adjustment was performed using the same intraoperative topographer. Results: At 12 months postoperatevely (suture in), data from 108 (64%) eyes were available. The mean refractive astigmatism was 3.53 D, and the mean topographical astigmatism was 4.7 D. At 18 months (suture out), data from 32 eyes (19.4%) were available, and at 24 months, data from 29 eyes (13.3%) were available. The mean refractive astigmatism was 3.39 D at 18 months and 3.47 D at 24 months. The mean topographic astigmatism was 2.30 D at 18 months and 1.76 D at 24 months. Mean best spectacle-corrected visual acuity (BSCVA) was 0.51 at 3 months, 0.63 at 12 months (suture in), 0.67 at 18 months (suture out), and 0.78 at 24 months postoperatively. Conclusions: The combination of intraoperative topography and a 24-bite single running suture resulted in a stable astigmatism throughout the follow-up period, even after suture removal. BSCVA reached a 20/40 level as early as 3 months postoperatively and continued to rise after suture removal. The stability of astigmatism and BSCVA shortened the postoperative visual rehabilitation time and provided a high quality of vision early in the postoperative period.

Purpose: To assess reproducibility of central corneal thickness (CCT) measurement by means of ultrasonic pachymetry. Methods: Fifty one volunteers underwent three sessions of CCT measurements, each consisting of three CCT measurements, performed by each of three different observers. Intra-and interobserver reproducibility was calculated by means of intraclass correlation coefficient (ICC). The expected range of variability between two independent evaluations was calculated using scatter plots of each test-retest difference against their mean. The standard deviation of the mean differences in the test-retest scores was used to describe the differences in the score spread. Results: The ICC ranges of the intra- and interobserver evaluations were 0.95-0.97 and 0.89-0.95 respectively; the expected variability was ≤ ± 1% and ≤ ± 2% respectively (95% confidence interval). Conclusions: The measurement of CCT by means of ultrasonic pachymetry is highly reproducible

Purpose To evaluate the sensitivity and specificity of optic disk examinations performed using the Moorfields regression analysis (MRA) of the Heidelberg Retina Tomograph (HRT) in differentiating normal from glaucomatous eyes. Design Retrospective cross-sectional study. Methods Five hundred and nineteen patients were included in the study for a total of 193 normal eyes, 213 with suspected glaucoma (primary open-angle glaucoma [POAG]), and 113 with POAG. The intervention consisted of optic disk imaging by means of HRT I. A mean of three repeated images was analyzed using version 2.01 software. The optic disk was classified as “normal/outside normal limits” on the basis of the MRA. The visual field was examined using the DS 24 II program (Humphrey perimeter), with a glaucomatous visual field being defined on the basis of an abnormal Glaucoma Hemifield Test and a statistically significant corrected pattern standard deviation greater than 2 dB. The results obtained with MRA were compared with those obtained using the multivariate discriminant analysis (MDA) provided in the HRT I. The main outcome measures were sensitivity, specificity, and positive and negative predictive values of HRT examination. Results The sensitivity and specificity of the HRT-MRA examination were, respectively, 74% and 94% (83% and 75% with MDA) when the patients with suspected POAG were excluded from the analysis; the figures were 74% and 85%, and 41% and 94% (83% and 64%, and 60% and 75% with MDA) when the same patients were included as being normal or having POAG. Conclusions In a broad clinical setting including normal subjects, patients with suspected POAG, and POAG patients, the HRT-MRA showed a high degree of diagnostic accuracy. The MRA was less sensitive but more specific than MDA. Greater diagnostic ability may be added by HRT-MRA examinations than by HRT-MDA to standard POAG diagnostic studies.