[Structural and functional features of the eye in Marfan syndrome. Report 2. Changes in the anatomical complex of the lens]. / Strukturno-funktsional'nye osobennosti glaza pri sindrome Marfana. Soobshchenie 2. Izmeneniya anatomicheskogo kompleksa khrustalika.

Analysis of lens changes in Marfan syndrome (MS), in addition to assessing the position of the lens itself, should include the possibility of examining its supporting and accommodative components (ciliary zonule and ciliary body), or what can be called the entire anatomical complex of the lens. Optical methods of studying the structures of the anterior segment of the eye, due to iris opacity, allow only to analyze the state of the lens within the natural or medically enlarged pupil width. Visualization of the structures located behind the iris is possible with the use of radiation diagnostic methods, in particular ultrasound biomicroscopy (UBM). PURPOSE: This study assesses the state of the anatomical complex of the lens in MS using UBM. MATERIAL AND METHODS: The study was carried out on clinical material previously used by us to analyze changes in the fibrous membrane of the eye in MS. At the first stage, the main (19 patients with MS, 38 eyes) and the control (24 patients with myopia, 48 eyes) groups were formed for comparative evaluation. The formed groups were standardized according to the age of the patients and the axial length of the eye. At the second stage, patients with MS were divided into subgroups depending on the absence or presence of biomicroscopic signs of ectopia lentis (22 and 16 eyes, respectively). For UBM, an ultrasound linear sensor with a scanning frequency of 50 MHz was used (Aviso device, Quantel Medical, France). Various biometric UBM indicators were determined: lens thickness, diameter of the lens, lens-axial length factor, iris-lens angle, iris-lens contact distance, posterior chamber depth, length of the fibers of ciliary zonule, thickness of the ciliary body, sclera-ciliary process angle. RESULTS: There are changes in the anatomical complex of the lens as a whole in MS (in the lens itself, the ciliary zonule, and the ciliary body), which are characterized by an increase in lens thickness and a decrease in the diameter of the lens, an increase in the length of the fibers of the ciliary zonule and a decrease in the thickness of the ciliary body. At the same time, the displacement of the lens detected by optical biomicroscopy (ectopia lentis) can be considered as an advanced stage of changes in the anatomical complex of the lens. CONCLUSION: UBM provides the possibility of full-fledged visualization of all components of the anatomical complex of the lens in terms of both diagnostics, and monitoring of changes in MS. The question of the advisability of including this method in the algorithm for diagnosing ocular manifestations in order to verify the MS remains open. Possible obstacles may be, on the one hand, related to the need for special and expensive equipment, and on the other hand, the absence of a generally accepted «normal¼ values of UBM indicators of the anatomical complex of the lens.

[Structural and functional features of the eye in Marfan syndrome. Report 1. Changes in the fibrous tunic of the eye]. / Strukturno-funktsional'nye osobennosti glaza pri sindrome Marfana. Soobshchenie 1. Izmeneniya fibroznoi obolochki.

Marfan syndrome (MS) is an orphan hereditary connective tissue disease associated with a mutation in the FBN1 gene, which pathological manifestations are characterized by polysystemic involvement. The fibrillin-1 protein is an integral component of the sclera and cornea of the eye, and in MS its structure is distrubed. PURPOSE: This study assesses potential structural and functional changes in the cornea and sclera of a patient with MS. MATERIAL AND METHODS: Two groups were formed, comparable in the axial length of the eye and age: the main group - 19 patients (38 eyes) with a verified diagnosis of MS, and the control group - 24 patients (48 eyes) with myopia of varying degrees. The results obtained from MS patients were analyzed depending on the absence or presence of ectopia lentis. In addition to measuring the basic ophthalmological parameters (refraction, axial length, visual acuity), topographic keratometry, anterior segment optical coherence tomography, and ocular response analyzer were used for structural and functional assessment of the cornea and sclera. RESULTS: In MS there was a statistically significant increase in the radius of curvature and a decrease in corneal refraction in the central zone compared to the control group. There were no significant differences in central corneal thickness, but there was a significant decrease in the thickness of the sclera in the limbal zone compared to the control group. There were no statistically significant changes in corneal hysteresis and corneal resistance factor in MS. CONCLUSION: This study confirmed the previously obtained data on the tendency of the optical power to reliably decrease in MS (flattening of the cornea). This symptom can be considered as a compensatory factor affecting clinical refraction, while the decrease in the thickness of the sclera - as the main reason for aaxial length elongation in MS. There were no clear patterns of dependence of the changes in the cornea and sclera analyzed in this study on the presence or absence of ectopia lentis. Changes in the lens, perhaps, should be regarded only as one of the potential components of the ocular symptom complex in MS.

Biometric and corneal characteristics in marfan syndrome with ectopia lentis.

PURPOSE: To describe the biometric and corneal characteristics of patients with Marfan Syndrome (MFS) and ectopia lentis. STUDY DESIGN: Observational, descriptive, prospective study. Subjects Individuals with MFS with ectopia lentis (EL). METHODS: Fourty-four eyes of 23 patients underwent Scheimpflug analysis using the Pentacam (Oculus, Wetzlar, Germany), axial length (AL) using the IOL master 700 (Carl Zeiss AG, Oberkochen, Germany), endothelial cell count (ECC) using the CEM-350 (NIDEK, Maihama, Japan) and corneal biomechanics evaluation with the Ocular Response Analyzer: ORA (Reichert Ophthalmic Instruments, Buffalo, New York, USA) and Corvis (Oculus, Wetzlar, Germany). Statistical analysis was performed using IBM SPSS Statistics 25.0. RESULTS: The direction of lens subluxation was most frequently supero-nasal 40.9% (18/44). Mean keratometry (Km) was 40.22±1.76 Diopters (D); mean corneal astigmatism was 1.68±0.83 D; total corneal aberrometric root mean square (RMS) was 2.237±0.795µm; higher-order aberrations (HOAs) RMS were 0.576±0.272µm; mean AL was 25.63±3.65mm; mean ECC was 3315±459cell/mm2; mean CBI was 0.13±0.24, mean TBI was 0.31±0.25, mean posterior elevation was 4.3±4.5µm; mean total corneal densitometry was 16.0±2.14 grayscale units (GSU). CONCLUSION: Increased axial length, flatter and thicker corneas with higher regular astigmatism, normal densitometry, normal corneal biomechanical indices and normal posterior elevation were observed in Marfan patients with EL.

Morphometric Assessment of the Ciliary Body in Patients With Marfan Syndrome and Ectopia Lentis: A Quantitative Study Using Ultrasound Biomicroscopy.

PURPOSE: To explore the biometric characteristics of the ciliary body in patients with Marfan syndrome (MFS) and ectopia lentis (EL). DESIGN: Cross-sectional study. METHODS: Seventy-two consecutive patients with MFS and EL and 72 nondiseased control subjects were recruited. Ciliary body biometric parameters such as ciliary muscle cross-sectional area at 2000 µm from the scleral spur (CMA2000), ciliary muscle thickness at 1000 µm from the scleral spur (CMT1000), and maximum ciliary body thickness (CBTmax) were measured from multiple directions with ultrasound biomicroscopy (UBM). The relationship between ciliary body parameters and other ocular characteristics was also evaluated. RESULTS: Average CMA2000, CMT1000, and CBTmax were 0.692 ± 0.015 mm2, 0.405 ± 0.010 mm, and 0.855 ± 0.023 mm in eyes of patients with MFS, respectively, and were significantly smaller than these values in control subjects (all P < .001). The prevalence of ciliary body thinning was 22.2% in the MFS group vs 0 in the control group (P < .001); eyes with more severe EL had smaller CMA2000 (P = .050), thinner CMT1000 (P = .022), and shorter CBTmax (P = .015). Patients with microspherophakia (MSP) had even smaller CMA2000 (P = .033) and CMT1000 (P = .044) than those without MSP. The most common subluxation direction was in the superonasal quadrant (n = 25; 39.7%), which probably correlates with the thinnest CMT1000 in the inferotemporal quadrant (P = .005). CONCLUSIONS: Patients with MFS and EL had thinner ciliary muscles, shorter ciliary processes, and a higher prevalence of ciliary body thinning, especially those with MSP. Both the extent and direction of subluxation were associated with ciliary body biometry..

Familial Ectopia Lentis: Looking Beyond Marfan's Syndrome.

Ectopia lentis has a myriad of causes, with Marfan's syndrome and homocystinuria being well-known causes. Here, we report two siblings with ectopia lentis and tall stature presenting with a diagnostic challenge. How to cite this article: Hussain SJ, Amalnath D, Kasthuri N, et al. Familial Ectopia Lentis: Looking Beyond Marfan's Syndrome. J Assoc Physicians India 2023;71(11):94-95.

Outcomes of three surgical approaches for managing ectopia lentis in Marfan syndrome.

OBJECTIVE: To investigate the clinical outcomes of three surgical approaches for ectopia lentis in Marfan syndrome (MS) patients who had undergone crystalline lens removal with posterior chamber intraocular lens (IOL) implantation techniques comprising the intrascleral fixation of IOL, sutured scleral fixation of IOL, and IOL implantation with the use of a Cionni capsular tension ring (CTR). METHODS: This is a retrospective comparative study, including 35 eyes of 21 patients who underwent the intrascleral fixation of IOL (group 1), scleral IOL fixation with the Z-suture (group 2), and IOL implantation with the use of a Cionni CTR (group 3) following crystalline lens removal. The surgical indications were as follows: no improvement in visual function after eyeglasses or contact lens application due to excessive irregular astigmatism and advanced crystalline lens decentration in which the edge of the crystalline lens came up to the optical axis, or dislocation of the crystalline lens resulting in aphakia and secondary glaucoma due to lens dislocation. The surgical outcomes and complications due to surgery were compared between the groups. RESULTS: The mean age of the patients in the study was 12.3 ± 8.7 years (5-32 years). There were 10 eyes in group 1, 13 eyes in group 2, and 12 eyes in group 3. Visual acuity improved significantly in each group after surgery. Ocular residual astigmatism did not differ significantly between the groups (p = 0.51). CONCLUSION: There were no significant differences between the three surgical approaches in the current study in terms of the postoperative results and complications.

Sutureless Scleral-Fixated Intraocular Lens Implantation in the Treatment of Congenital Lens Subluxation Related to Marfan Syndrome.

PURPOSE: To evaluate the efficacy and safety of bimanual capsulorhexis combined with sutureless scleral-fixated intraocular lens (IOL) implantation in children diagnosed as having Marfan syndrome. METHODS: The study included 14 eyes with subluxated lenses of 7 children who were diagnosed as having Marfan syndrome and underwent bimanual capsulorhexis combined with sutureless scleral-fixated IOL implantation by the same surgeon between 2015 and 2019 at the University of Health Sciences, Kartal Dr. Lütfi Kirdar City Hospital's Eye Department. RESULTS: The mean preoperative and postoperative uncorrected visual acuity was 1.47 ± 0.41 and 0.42 ± 0.15 logarithm of the minimum angle of resolution (logMAR), respectively (P = .001). The preoperative best corrected visual acuity (BCVA) ranged from 1.30 to 0.40 logMAR with a mean value of 0.81 ± 0.30 logMAR. Postoperatively, all patients had an increase in the BCVA with a mean value of 0.20 ± 0.11 logMAR, which was statistically significant (P = .001). The mean preoperative and postoperative spherical equivalent was -9.69 ± 4.59 and -0.27 ± 1.21 diopters, respectively. CONCLUSIONS: Despite the small number of patients in this study, good visual results and a low complication rate were obtained in patients with ectopic lens. The long-term IOL status in patients who have undergone sutureless scleral-fixated IOL implantation will make it possible to better evaluate the safety and applicability of the technique. [J Pediatr Ophthalmol Strabismus. 2021;58(6):401-406.].

Exome sequencing and functional studies in zebrafish identify WDR8 as the causative gene for isolated Microspherophakia in Indian families.

Isolated Microspherophakia (MSP) is an autosomal recessive disorder characterized by a smaller than normal spherical lens. Till date, LTBP2 is the only gene shown to cause MSP. We used homozygosity mapping and whole-exome sequencing and identified a homozygous mutation, c.1148C > T (p.Pro383Leu), in the WDR8 (or WRAP73) gene in two Indian MSP families. In vitro experiments showed that the missense mutation renders the protein unstable. WDR8 is a centriolar protein that has important roles in centrosomal assembly, spindle pole formation and ciliogenesis. Co-immunoprecipitation experiments from HeLa cells indicated that the mutation interferes with the interaction of WDR8 with its binding partners. In zebrafish, both morpholino-mediated knockdown and CRISPR/Cas knockout of wdr8 resulted in decreased eye and lens size. The lack of wdr8 affected cell cycle progression in the retinal cells, causing a reduction in cell numbers in the retina and lens. The reduction in eye size and the cell cycle defects were rescued by exogenous expression of the human wild-type WDR8. However, the human mutant WDR8 (p.Pro383Leu) was unable to rescue the eye defects, indicating that the missense mutation abrogates WDR8 protein function. Thus, our zebrafish results suggested that WDR8 is the causative gene for MSP in these Indian families.

Visual outcomes of lens subluxation surgery with Cionni modified capsular tension rings in Marfan syndrome.

Marfan syndrome (MFS) is a hereditary disease with an incidence of 0.3% in the general population. Approximately 60% of MFS patients with FBN1 gene mutation will suffer ectopia lentis (EL) from the age of 3. With the development of EL, severe loss of vision will accrue because of lens tilt and glaucoma. Cionni modified capsular tension rings (MCTR) has been applied in the surgery for EL in MFS patients. To evaluate visual acuity and safety of using MCTR during lens subluxation surgery in MFS patients, 66 MFS patients (110 eyes) were included in our study, with the mean duration of follow-up of 4.7 months (SD 1.76 months). The capsular bags were preserved in 101 eyes (91.81%) with MCTR implantation. There was an overall significant improvement in BCVA at 1-month follow-up which was maintained at 3 months. Multivariable linear regression revealed that older age at first visit was associated with greater postoperative BCVA at the 1-month follow-up (P = 0.007). A significant difference was found between different degrees of lens subluxation and the length of surgical time and complications. At follow-up, only two eyes (1.98%) were identified to have developed retinal detachments. In conclusion, better visual outcomes can be achieved when patients received an early operation with MCTR implantation.

Ocular manifestations in classic homocystinuria.

BACKGROUND: Classic homocystinuria (HCU), or cystathionine beta-synthase (CBS) deficiency, is a rare inborn error of methionine metabolism. Main clinical features may include skeletal and vascular manifestations, developmental delay, intellectual disability and eye disorders. MATERIAL AND METHODS: This is an observational and retrospective study aiming at describing eye abnormalities presented by a cohort of late-diagnosed HCU patients. Data regarding ophthalmological evaluation included visual acuity, refraction, biomicroscopy, Perkins tonometry, fundus examination, retinography, biometry, ocular ultrasound, optical coherence tomography, anterior segment photography and topography. RESULTS: Ten patients with HCU (20 eyes) were included. The most frequent findings were ectopia lentis(n = 20) and myopia (n = 9). Biometry, ultrasound, OCT and topography findings were available for four patients. One patient had keratoconus; one had abnormal retinal pigmentation; and two had lens surgery scars with irregular astigmatism. CONCLUSIONS: Eye abnormalities are very frequent in late-diagnosed HCU patients. The presence of ectopia lentis should always raise the diagnostic hypothesis of HCU.

Novel double-flanged technique for managing Marfan syndrome and microspherophakia.

A new technique for fixating the capsular bag in patients with ectopia lentis is presented. In this technique, the capsulorhexis is performed using a femtosecond laser, followed by the insertion of a standard capsular tension ring to redistribute capsular forces. The nucleus is hydroprolapsed into the anterior chamber and nuclear disassembly is performed above the iris plane to reduce zonular stress. Finally, a 5-0 polypropylene monofilament is used to fixate a capsular tension segment and subluxated capsular bag. This novel double-flanged method, achieved with cautery, does not require direct suturing of the monofilament on the sclera. This article describes the use of this new technique in 3 eyes, 2 in patients with Marfan syndrome and 1 in a patient with microspherophakia.

Bimanual irrigation-aspiration for ectopia lentis and use of a small incision for 4-point scleral-sutured foldable intraocular lens and anterior vitrectomy in patients with Marfan syndrome.

Purpose: This study evaluated bimanual intracapsular irrigation-aspiration for ectopia lentis with use of a small incision for 4-point scleral fixation of a foldable posterior-chamber intraocular lens (IOL) and anterior vitrectomy in patients with Marfan syndrome. Methods: We performed a retrospective study of 18 eyes from 10 patients with Marfan syndrome who underwent surgical intervention for ectopia lentis at our clinic between July 2012 and September 2018. In this study, intraoperative and postoperative complications, uncorrected visual acuity, best-corrected visual acuity, spherical equivalent, intraocular pressure, and endothelial cell density were evaluated. Results: No intraoperative complications were reported. In all cases, early postoperative evaluation revealed a clear cornea, round pupil, and well-centered IOL. Mean logMAR uncorrected visual acuity improved from 1.09 preoperatively to 0.56 postoperatively (P < 0.05). Mean logMAR best-corrected visual acuity improved from 0.45 preoperatively to 0.17 postoperatively (P < 0.05). Aside from transient ocular hypertension, no postoperative complications were reported. Conclusion: The combined surgical technique presented above yields excellent visual outcomes with an extremely low incidence of complications. This approach is simple, safe, and effective in the treatment of ectopia lentis in patients with Marfan syndrome.

Visual outcome and surgical results in children with Marfan syndrome.

IMPORTANCE: To determine visual and surgical results in children with Marfan syndrome. BACKGROUND: Marfan syndrome involves ocular complications which can lead to visual disturbance and amblyopia. Data about the visual and surgical results in children with Marfan syndrome is vital for the clinical management of these patients. DESIGN: Retrospective data analysis. PARTICIPANTS: Eighty-two eyes of 41 patients with a genetically proved diagnosis of Marfan syndrome. METHODS: Medical records of patients with Marfan syndrome were reviewed between 2007 and 2017. Ocular complications, visual acuity (VA) of patients with/without lensectomy and surgical method were evaluated. MAIN OUTCOME MEASURES: VA outcomes of patients with Marfan syndrome with/without surgical repair of ectopia lentis. RESULTS: In 27 (66%) of the 41 patients a bilateral subluxation of the lens was visible and 14 (52%) patients received lensectomy. The mean age at initial presentation was 12.3 ± 9 years and mean follow-up was 3 years (range 1-7). VA varied from 1.2 to -0.1 logMAR at first examination. At initial presentation, mean VA was 0.1 ± 0.7 logMAR in patients with a normal lens status (n = 14) and 0.3 ± 0.5 logMAR in patients with subluxation of the lens (n = 27) (P < .01). VA improved from 0.2 ± 0.5 logMAR to 0.1 ± 0.5 logMAR (P = .06) in children with subluxation of the lens who did not need a lensectomy (n = 12) and from 0.5 ± 0.5 logMAR to 0.2 ± 0.5 logMAR (P = .02) in patients who were referred to lensectomy with/without secondary lens implantation. CONCLUSIONS AND RELEVANCE: In Marfan syndrome subluxation of the lens was found in the majority of children. Improvement of VA resulted in children with subluxation of the lens and following lensectomy.

Microcornea and bilateral ectopia lentis in an infant: unusual severe ocular presentation of neonatal Marfan syndrome.

We present an unusual case of microcornea, bilateral spontaneous dislocation of lenses, and anomalous optic disks in a 7-week-old girl in whom a systemic diagnosis of Marfan syndrome had not yet been confirmed at presentation. The causes and differential diagnoses of this condition are discussed, and the literature on ocular manifestations of neonatal Marfan syndrome is reviewed.