Description of a new family with cryopyrin-associated periodic syndrome: risk of visual loss in patients bearing the R260W mutation.

OBJECTIVE: The aim of this study was to describe a family with cryopyrin-associated periodic syndrome (CAPS) in which the disease was unveiled after the ophthalmologic evaluation. METHODS: Family and personal histories from each of the patients were recorded. Each underwent a full ophthalmological examination along with the physical examination. The mutational analysis of the NLRP3 gene was performed by means of direct sequencing. RESULTS: The proband was admitted during an episode of unilateral anterior uveitis. She had a history of recurrent red eye and had been suffering episodes of skin rash and arthralgia induced by cold since childhood. At examination, she showed a reticulated corneal mid-stroma. Her mother and her younger sister also suffered from relapsing episodes of skin rash and fever triggered by cold as well as flares of red eye. They had developed premature hearing loss. In both cases, opacities in the corneal mid-stroma were evidenced with a slit lamp. The genetic analysis detected the heterozygous germline p.R260W mutation in the NLRP3 gene in the three women, confirming the diagnosis of CAPS. Treatment with anakinra resulted in complete remission of flares. CONCLUSION: In this family, a structural NLRP3 mutation was associated with classic MuckleWells features of different degrees of severity. Interstitial keratitis with corneal opacification, usually ascribed to neonatal-onset multisystem inflammatory disease, was found. We underscore that ocular involvement in MuckleWells syndrome should be carefully assessed, since it can lead to visual impairment.

Optical Evaluation of Intracorneal Ring Segment Surgery in Keratoconus.

Purpose: The purpose of this study was to assess the impact of different intracorneal ring segments (ICRS) combinations on corneal morphology and visual performance on patients with keratoconus. Methods: A total of 124 eyes from 96 patients who underwent ICRS surgery were analyzed and classified into 7 groups based on ICRS disposition and the diameter of the surgical zone (5- and 6-mm). Pre- and postoperative complete ophthalmological examinations were conducted. Corneal geometry, volume, and symmetry were studied. Zernike polynomials were used to build a virtual ray-tracing model to evaluate optical aberrations and the Visual Strehl (VS). Results: ICRS induced significant flattening across the cornea, being more pronounced on the anterior (+0.38 mm, P < 0.001) than on the posterior (+0.15 mm, P < 0.001) corneal radius. Asphericity experienced a larger change for a 6-mm surgical zone diameter (from -1.23 ± 1.1 to -1.86 ± 1.2, P < 0.001) than for a 5-mm zone (from -1.99 ± 1.1 to -2.10 ± 1.5, P = 0.536). Mean astigmatism was reduced by 2.05 D (P < 0.001). Combination four was the most effective in reducing astigmatism. Coma decreased by 30% on average and combination one produced an average reduction by 51% (P < 0.05). Patients experienced significant improvement in visual performance, best corrected visual acuity increased from 0.57 ± 0.21 to 0.69 ± 0.21 and VS changed from 0.049 ± 0.02 to 0.065 ± 0.041. Conclusions: ICRS combinations implanted within 5 mm diameter zone are more effective in flattening the cornea, whereas those implanted on 6 mm diameter are as effective in reducing astigmatism and are a good choice if the asymmetry and the intended flattening are smaller. Combinations with asymmetrical implants are the best option to regularize corneal surface. Translational Relevance: This study uses methods and metrics of optical research applied to daily clinical practice.

Correction: Assesment of the QuickSee wavefront autorefractor for characterizing refractive errors in school-age children.

[This corrects the article DOI: 10.1371/journal.pone.0240933.].

Intraocular leucocyte subpopulations analysis by multiparametric flow cytometry in human uveitis.

PURPOSE: The aim of this study was to describe the cellular infiltrate in aqueous and vitreous samples of patients with uveitis analysed by multiparametric flow cytometry. METHODS: This is a retrospective analysis of aqueous and vitreous samples analysed by flow cytometry for diagnostic purposes, in cases of masquerade syndromes and infectious and non-infectious uveitis. Data collected included demographics, anatomical classification of uveitis, phenotypic diagnosis, anterior chamber cells grading, vitreous haze and time of follow-up since presentation to sample obtained. RESULTS: Thirty-one samples (17 aqueous and 14 vitreous fluids) from 31 patients, 18 men, were analysed. The mean age at the time of sample collection was 60.23±17.03 years. The most frequent anatomical classification was panuveitis (14 of 31). T cells accounted for the main cellular component in the majority of the samples (10 of 13 aqueous samples; 7 of 14 in vitreous samples). CD4:CD8 ratios ranged from 0.21 to 16.3 in the case of aqueous samples and from 0.5 to 9.7 in the case of vitreous samples. DISCUSSION: Flow cytometry analysis of aqueous and vitreous samples from patients with uveitis could provide insight into the pathogenesis of human uveitis and help develop accurate animal models which better mimic human disease.

Long term follow-up and effect of immunosuppression in acute zonal occult outer retinopathy.

Acute zonal occult outer retinopathy (AZOOR) is a rare syndrome characterized by sudden onset of photopsia, scotomas, and abnormal electrophysiological tests, predominantly affecting young women. Although its pathogenesis remains unknown, auto-reactivity to retinal components is thought to mediate tissue damage. A 42-year-old woman presented with symptoms and examination consistent with the diagnosis of AZOOR. She was treated with azathioprine for 5 years. In spite of the immunosuppressive treatment, clear progression in the visual field, autofluorescence, electrophysiological tests and optical coherence tomography was observed. Treatment with intravenous immunoglobulins (IVIg) and subcutaneous Abatacept was subsequently started with little efficacy. Hereby, we present a case of progressive AZOOR despite aggressive immunosuppression with 10-year follow up. Currently, there is no consensus regarding management of AZOOR, and the convenience of administering aggressive immunosuppression remains uncertain.

Interaction of Monochromatic and Chromatic Aberrations in Pseudophakic Patients.

PURPOSE: To measure monochromatic aberrations at various wavelengths in eyes implanted with the Clareon monofocal aspheric intraocular lens (IOL) (Alcon Laboratories, Inc., Fort Worth, TX). The authors estimated longitudinal chromatic aberration (LCA), modulation transfer functions (MTFs), and the impact of interactions between chromatic and monochromatic aberrations on retinal image quality. METHODS: Ten patients (age: 68.4 ± 3.21 years) were measured in two experiments: (1) Hartmann-Shack wave aberrations at five visible wavelengths (480 to 700 nm) and (2) best subjective focus at each wavelength. Objective and psychophysical LCAs were obtained from the Zernike defocus and psychophysical best focus, respectively. MTFs were calculated for the closest wavelengths to the peak sensitivity of the three cone classes (S [480 nm], M [555 nm], and L [564 nm]) using the measured aberrations and chromatic difference of focus. The degradation produced by LCA was estimated as the visual Strehl ratio for green divided by the visual Strehl ratio for blue and red. RESULTS: The root mean square for higher order aberrations (HOAs) ranged from 0.0622 to 0.2084 µm (700 nm, 4.3-mm pupil). Monochromatic visual Strehl ratio was above 0.35 in all patients. LCA was 1.23 ± 0.05 diopters (D) (psychophysical) and 0.90 ± 0.11 D (objective). Visual Strehl ratio decreased by a factor ranging from 1.38 to 3.82 on chromatic defocus from green to blue. There was a significant correlation between native visual Strehl ratio and the degradation produced by LCA (ie, visual Strehl555/visual Strehl480). CONCLUSIONS: The Clareon IOL compensates for spherical aberration, with postoperative wave aberrations dominated by astigmatism and other HOAs, being highly subject-dependent. The impact of LCA in blue is largely dependent on the magnitude of monochromatic aberrations. [J Refract Surg. 2020;36(4):230-238.].

Assesment of the QuickSee wavefront autorefractor for characterizing refractive errors in school-age children.

PURPOSE: To assess the performance of an open-view binocular handheld aberrometer (QuickSee) for diagnosing refractive errors in children. METHODS: 123 school-age children (9.9 ± 3.3 years) with moderate refractive error underwent autorefraction (AR) with a standard desktop device and subjective refraction (SR), with or without cycloplegia to determine their eyeglass prescription. Measurements with QuickSee (QS) were taken in 62 of these patients without cycloplegia (NC), and in 61 under cycloplegia (C). Differences in refraction values (AR vs SR vs QS) as well as the visual acuity (VA) achieved by the patients with each method (QS vs SR) were used to evaluate the performance of the device in measuring refractive error. RESULTS: The spherical equivalent refraction obtained by QS agreed within 0.5 D of the SR in 71% (NC) and 70% (C) of the cases. Agreement between the desktop autorefractor and SR for the same threshold was of 61% (NC) and 77% (C). VA resulting from QS refractions was equal to or better than that achieved by SR procedure in 77% (NC) and 74% (C) of the patients. Average improvement in VA with the QS refractions was of 8.6 and 13.4 optotypes for the NC and C groups respectively, while the SR procedure provided average improvements of 8.9 (NC) and 14.8 (C) optotypes. CONCLUSIONS: The high level of agreement between QuickSee and subjective refraction together with the VA improvement achieved in both study groups using QuickSee refractions suggest that the device is a useful autorefraction tool for school-age children.

Diagnostic Sensitivity of Different Reference Bodies When Using Scheimpflug Tomography in a Myopic Population with Keratoconus.

PURPOSE: To establish which reference body offers the greatest sensitivity in keratoconus (KC) diagnosis, obtain normative data for the myopic population with toric ellipsoid reference bodies, and determine the cutoff points for a population with KC. METHODS: A retrospective, observational study of the entire Scheimpflug tomographer database of the Fundación Jiménez Díaz in Madrid was conducted to identify a normal myopic and a KC myopic population. Three different reference bodies were tested on all patients: best fit sphere (BFS), best fit toric ellipsoid with fixed eccentricity (BFTEFE), and best fit toric ellipsoid (BFTE). Anterior and posterior elevation measurements at the apex and thinnest point were recorded, as well as the root mean square of posterior elevations (RMS-P). Normative data were extracted, and receiver operating characteristic (ROC) curves were generated to obtain cutoff points between the normal and KC population. RESULTS: A total of 301 eyes were included, comprising 219 normal myopic and 82 myopic KC eyes. BFS and BFTEFE produced the best results when measuring posterior elevation at the thinnest point. BFTE had better sensitivity with the RMS-P. From all measurements, best sensitivity (100%) was achieved with a cutoff point of 8 µm of posterior elevation at the thinnest point using the BFTEFE. BFTE was found to hide the cone in certain patients. CONCLUSIONS: Posterior elevation measured at the thinnest point with a BFTEFE is the best-performing parameter and, therefore, is recommended to discriminate between normal and KC patients within a myopic population.

Evaluation of the True Wavefront Aberrations in Eyes Implanted With a Rotationally Asymmetric Multifocal Intraocular Lens.

PURPOSE: Standard evaluation of aberrations from wavefront slope measurements in patients implanted with a rotationally asymmetric multifocal intraocular lens (IOL), the Lentis Mplus (Oculentis GmbH, Berlin, Germany), results in large magnitude primary vertical coma, which is attributed to the intrinsic IOL design. The new proposed method analyzes aberrometry data, allowing disentangling the IOL power pupillary distribution from the true higher order aberrations of the eye. METHODS: The new method of wavefront reconstruction uses retinal spots obtained at both the near and far foci. The method was tested using ray tracing optical simulations in a computer eye model virtually implanted with the Lentis Mplus IOL, with a generic cornea or with anterior segment geometry obtained from custom quantitative spectral-domain optical coherence tomography in a real patient. The method was applied to laser ray tracing aberrometry data at near and far fixation obtained in a patient implanted with the Lentis Mplus IOL. RESULTS: Higher order aberrations evaluated from simulated and real retinal spot diagrams following the new reconstruction approach matched the nominal aberrations (approximately 98%). Previously reported primary vertical coma in patients implanted with this IOL lost significance with the application of the proposed reconstruction. CONCLUSIONS: Custom analysis of ray tracing-based retinal spot diagrams allowed decoupling of the true higher order aberrations of the patient's eye from the power pupillary distribution of a rotationally asymmetric multifocal IOL, therefore providing the appropriate phase map to accurately evaluate through-focus optical quality. [J Refract Surg. 2017;33(4):257-265.].

Toward New Engagement Paradigms For Intraocular Lenses: Light-Initiated Bonding of Capsular Bag to Lens Materials.

PURPOSE: Successful intraocular lens procedures, that is, implantation of accommodating intraocular lenses (A-IOL), require firm engagement of the IOL haptics to the capsular bag. We evaluated the use of photochemical bonding to engage IOL materials to the capsular bag. METHODS: Freshly enucleated eyes of New Zealand rabbits were used in two types of photobonding experiments using Rose Bengal (RB) photoinitiation and green light (532-nm) irradiation. First, RB-stained capsular bag strips were photobonded ex vivo to IOL polymer [poly(2-hydroxyethyl methacrylate) pHEMA] strips in an atmosphere of air and of nitrogen. Second, IOLs were implanted intracapsularly and photobonded intraocularly. Irradiation times were between 30 and 180 seconds, and laser irradiance was between 0.25 and 0.65 W/cm(2). The strength of the bonding was tested using a custom-developed uniaxial extensiometry system and the breakage load (the load that caused breakage per bonded area) was calculated. RESULTS: The breakage load of ex vivo capsule-pHEMA bonds increased exponentially with irradiation time, using 0.45 W/cm(2). In air, the average breakage load across all conditions was 1 g/mm(2) and 1.6 times lower than that in a nitrogen atmosphere. Intraocularly, RB-stained IOLs were strongly photobonded to the capsule bag with breakage loads > 0.8 g/mm(2). CONCLUSIONS: Breakage of the photobonded linkage between IOL material and capsular bag required loads substantially greater than the maximum force of ciliary muscle, suggesting that this technology may introduce a new paradigm for engagement of A-IOLs. The bonding produced in air was stronger than that in nitrogen atmosphere, suggesting that oxygen is involved in the chemical mechanism for photobonding.

Ocular and optical coherence tomography-based corneal aberrometry in keratoconic eyes treated by intracorneal ring segments.

PURPOSE: To analyze corneal and total aberrations using custom-developed anterior segment spectral optical coherence tomography (OCT) and laser ray tracing in keratoconic eyes implanted with intracorneal ring segments (ICRS). DESIGN: Evaluation of technology. Prospective study. Case series. METHODS: Nineteen keratoconic eyes were measured before and after ICRS surgery. Anterior and posterior corneal topographic and pachymetric maps were obtained pre- and postoperatively from 3-dimensional OCT images of the anterior segment, following automatic image analysis and distortion correction. The pupil center coordinates were used as reference for estimation of corneal aberrations. Corneal aberrations were estimated by computational ray tracing on the anterior and posterior corneal surfaces. Total aberrations were measured using a custom-developed laser ray tracing aberrometer. Corneal and total aberrations were compared in 8 eyes pre- and postoperatively for 4-mm pupils. RESULTS: Total and corneal aberrations were highly correlated. Average root mean square of corneal and total high-order aberrations (HOAs) were 0.78 ± 0.35 µm and 0.57 ± 0.39 µm preoperatively, and 0.88 ± 0.36 µm and 0.53 ± 0.24 µm postoperatively (4-mm pupils). The anterior corneal surface aberrations were partially compensated by the posterior corneal surface aberrations (by 8.3% preoperatively and 4.1% postoperatively). Astigmatism was 2.03 ± 1.11 µm preoperatively and 1.60 ± 0.94 µm postoperatively. The dominant HOA aberrations both pre- and postoperatively were vertical coma (Z3(-1)), vertical trefoil (Z3(-3)), and secondary astigmatism (Z4(4)). ICRS decreased corneal astigmatism by 27% and corneal coma by 5%, but on average, the overall amount of HOA did not decrease significantly with ICRS treatment. CONCLUSIONS: OCT is a reproducible technique to evaluate corneal aberrations. OCT-based corneal aberrations and ocular aberrations show a high correspondence in keratoconic patients before and after ICRS implantation. ICRS produced a decrease in astigmatism, but on average did not produce a consistent decrease of HOAs.

Quantitative OCT-based longitudinal evaluation of intracorneal ring segment implantation in keratoconus.

PURPOSE: To characterize the geometrical properties of keratoconic corneas upon intracorneal ring segments (ICRS) implantation, using custom-developed optical coherence tomography (OCT). METHODS: Ten keratoconic corneas were measured pre- and post-ICRS surgery (7, 30, and 90 days). Corneal topographic and pachymetric maps were obtained from three-dimensional (3D) images acquired with OCT, provided with custom algorithms for image analysis, distortion correction, and quantification. The 3D positioning of the ICRS was also estimated longitudinally, relative to the pupil center and iris plane. RESULTS: Preoperatively, the average corneal radii of curvature were 7.02 ± 0.54 mm (anterior) and 5.40 ± 0.77 mm (posterior), and the minimum corneal thickness was 384 ± 60 µm. At 90 days, the average corneal radii of curvature were 7.26 ± 0.53 mm (anterior) and 5.44 ± 0.71 mm (posterior), and the minimum corneal thickness was 396 ± 46 µm. ICRS implantation produced a significant decrease of corneal power (by 1.71 ± 1.83 diopters [D] at 90 days). Corneal irregularities (defined by high order Zernike terms of the corneal elevation maps) and the corneal thickness distribution decreased in some patients and increased in others. The 3D ICRS depth matched the planned ICRS depth well (within 23.93 ± 23.49 µm). On average, ICRS showed an overall tilt of -6.8 ± 2.6° (temporal) and -2.1 ± 0.8° (superior) at 7 days. CONCLUSIONS: Spectral OCT (sOCT) provided with distortion correction and analysis tools, is an excellent instrument for evaluating the changes produced by ICRS in keratoconic corneas, and for analyzing the 3D ICRS position during the follow up. ICRS produced flattening on the anterior corneal surface, although the benefit for corneal surface regularization varied across patients.

Quantitative OCT-based corneal topography in keratoconus with intracorneal ring segments.

Custom high-resolution high-speed anterior segment spectral domain Optical Coherence Tomography (OCT) was used to characterize three-dimensionally (3-D) corneal topography in keratoconus before and after implantation of intracorneal ring segments (ICRS). Previously described acquisition protocols were followed to minimize the impact of the motions of the eye. The collected set of images was corrected from distortions: fan (scanning) and optical (refraction). Custom algorithms were developed for automatic detection and classification of volumes in the anterior segment of the eye, in particular for the detection and classification of the implanted ICRS. Surfaces were automatically detected for quantitative analysis of the corneal elevation maps (fitted by biconicoids and Zernike polynomials) and pachymetry. Automatic tools were developed for the estimation of the 3-D positioning of the ICRS. The pupil center reference was estimated from the segmented iris volume. The developed algorithms are illustrated in a keratoconic eye (grade III) pre- and 30 days post-operatively after implantation of two triangular-section, 0.3-mm thick Ferrara ring segments. Quantitative corneal topographies reveal that the ICRS produced a flattening of the anterior surface, a steepening of the posterior surface, meridional differences in the changes in curvature and asphericity, and increased symmetry of the anterior topography. Optical distortion correction through the ICRS (of a different refractive index from the cornea) allowed accurate pachymetric estimates, which showed increased thickness in the ectatic area as well as in peripheral corneal areas. Automatic tools allowed estimation of the depth of the implanted ICRS ring, as well as its rotation with respect to the pupil plane. Anterior segment sOCT provided with fan and optical distortion correction and analysis tools is an excellent instrument for evaluating and monitoring keratoconic eyes and for the quantification of the changes produced by ICRS treatment.

Sympathetic ophthalmia in HIV infection. A clinicopathological case report.

BACKGROUND: The purpose of this study is to report a case of sympathetic ophthalmia (SO) in an HIV-infected patient on treatment with highly active antiretroviral therapy (HAART) 9 years after a penetrating eye injury. METHODS: The study utilized clinical course and histopathological findings. RESULTS: Histopathology of the enucleated right eye showed a predominantly lymphocytic inflammatory infiltration with some plasma cells and epithelioid granulomata in the choroid, suggesting the diagnosis of SO. CONCLUSIONS: SO seems to be driven by T lymphocytes, specifically by the CD4 subset of T cells. HIV-infected individuals suffer a decline in CD4 T cell numbers, leading to an acquired immunodeficiency that could halt the development of the inflammatory reaction responsible for SO. The restoration of the CD4 counts by HAART therapy makes HIV-infected individuals as susceptible to SO as non-infected ones. To the best of our knowledge, there are no cases of SO in HIV-infected patients reported in the literature.

Aparición de incomitancia lejos-cerca y de un componente acomodativo en la endotropia congénita tratada con toxina botulínica / Appearance of incomitance far-near and accommodative component in congenital esotropia treated with botulinum toxin

Objetivo: Este trabajo intenta estimar la aparición de inconcomitancia lejos-cerca y de un componente acomodativo en pacientes con endotropia congénita tratados con toxina botulínica. Métodos: Para ello hemos realizado un estudio retrospectivo de 26 pacientes con endotropia congénita, menores de tres años, tratados con TB sin I-LC ni componente acomodativo al inicio. El 42 por ciento de los pacientes se corrigió con toxina botulínica. La densidad de incidencia de I-LC fue de 0,079 pacientes-año. Resultados: Un 42,31 por ciento de los pacientes desarrollaron distinto grado de componente acomodativo. La aparición de ambos factores puede condicionar nuestras indicaciones quirúrgicas.

Purpose: Estimate the presence of convergence excess and refractive deviation in a group of patients with infantile esotropia treated with botulinic toxin. Method: Retrospective analysis of 26 patients with infantile esotropia treated with botulinic toxin before the age of three without convergence excess or refractive factor in their deviation. Results: 42 percent were controlled with botulinic toxin. The subsequent incidence of convergence excess was 0,079 patients/year. 42,31 percent of patients developed some degree of refractive component in their deviation. Both factors can modify our surgical indications.

Modificación del estrabismo vertical tras inyección de toxina botulínica A en la endotropía infantil / Modification of vertical strabismus after injection of botulinum toxin A in children esotropia

Introducción y objetivos: Analizar la modificación del estrabismo vertical tras la corrección de la endotropía con Toxina Botulínica (TB). Métodos: 51 endotropías consecutivas, tratadas con TB por debajo de 36 meses de edad. Resultados: 51.85 por ciento de las endotropías congénitas (EC) y 12.5 por ciento de las endotropías adquiridas (ETA) requirieron cirugía vertical. Cuando se corrigió la desviación horizontal, se redujo la necesidad de cirugía vertical a 38.51 por ciento (EC) y 4.54 por ciento (ETA) respectivamente. También se modificaron los patrones alfabéticos. Conclusiones: Se debe ser cauto en la indicación de la cirugía vertical asociada a un cuadro horizontal en la primera infancia.

Introduction and objectives: To study changes in vertical strabismus following treatment of esotropia using Botulinum Toxin. Methods: Fifty one consecutive patients with esotropia treated with Botulinum Toxin at the age of 36 months or less. Results: 51.85 percent of congenital esotropias (CE) and 12.5 percent of acquired esotropias (AET) required vertical surgery. When the horizontal deviation was completely corrected the requirement for vertical surgery was reduced to 38.51 percent (CE) y 4.54 percent (AET) respectively. Alphabet patterns were also affected. Conclusions: One should be cautious about the indications for vertical surgery associated with esotropia in early infancy.