Unusual presentation of cornea verticillata with intravitreal methotrexate in a case of primary intraocular lymphoma

A 56-year-old woman presented with floaters and diminution of vision in the right eye for 1 week. On examination, visual acuity was 20/400 in the right eye and 20/60 in the left eye. Indirect ophthalmoscopy revealed vitritis in the right eye and subretinal deposits in both eyes. Vitreous biopsy of the right eye revealed large B-cell-type primary intraocular lymphoma and the patient underwent multiple intravitreal methotrexate injections (400 μg/0.1 mL) in the right eye and systemic chemotherapy for bilateral disease. Following biweekly injections of methotrexate, her visual acuity improved considerably from 20/400 to 20/60 with resolution of vitritis. However, following eighth dose of intravitreal methotrexate, she experienced visual decline to 20/120 along with photophobia, redness and watering. Whorl-shaped opacities, limbitis and corneal haze were noted on slit-lamp examination. Intravitreal methotrexate was stopped, and the patient was started on frequent topical lubricants, loteprednol, topical folinic acid and oral folic acid. Complete resolution of corneal toxicity was observed at 3 weeks and the injections were suspended as there was no recurrence at 6 months follow-up.

The Importance of Molecular Testing for the Diagnosis of Fabry Disease Manifested by Cornea Verticillata Only

Aims: To describe a Fabry disease, that it’s diagnosis was only possible through the molecular test Presentation of Case: L.A.P. female, 42 years old, lawyer, seen by the ophthalmology department for routine consultation only with refractive complaints. Fundus of the eye: Mild narrowing with increased vascular brightness and presence of pathological arteriovenous crossings. The rest of the exam was within normal limits. Therefore, a genetic test with the dosage of the α-Gal enzyme was requested, which evidenced the alteration in it, confirming the diagnosis of Fabry disease. Discussion: A Fabry Disease (FD) is an inborn error of glycosphingolipid (GL) metabolism, resulting from deficient activity of the enzyme alpha-galactosidase A (α -Gal). It has X-chromosome-linked inheritance, affecting mainly males, with an estimated prevalence of 1:40,000 males. The expression of the disease in heterozygous female patients can vary from an asymptomatic condition to a severe systemic disease, like that which occurs in men. Conclusions: The ophthalmological examination played an important role in the diagnosis, as this change is highly suggestive of the disease, in order to avoid erroneous and late diagnoses that can cause consequences for patients with this condition.

Corneal densitometry: a potential indicator for early diagnosis of Fabry disease

Purpose To assess corneal densitometry in patients with Fabry disease (FD) and to compare corneal densitometry differences in FD patients to different corneal manifestations. Methods Ten participants (20 eyes) with FD and 10 age-matched healthy volunteers (20 eyes) were recruited. All participants were assessed by standardized ophthalmic examinations and the corneal densitometry analysis by Pentacam HR. Densitometry measurements were analyzed in standardized grayscale units. Results Seven patients developed conjunctival vessel tortuosity, cornea verticillata appeared in 6 patients, and two patients had Fabry cataract. Retinal vessel tortuosity occurred in 4 patients, and dilation of retinal vessels appeared in 3 patients, all symptoms occurred in both eyes. The first diagnosis of FD up to examination was 4.7 ± 3.23 years, and first ERT up to examination was 2.6 ± 2.27 years. The initial time to diagnosis was negatively related to the corneal densitometry value of the 0–2-mm (r = − 0.556, p = 0.011) and 2–6-mm (r = − 0.482, p = 0.032) zones in the posterior layer. FD group have significantly higher corneal densitometry in anterior 0–2-mm zone and 2–10-mm zone anterior and posterior layer than the control group (p ≤ 0.035, respectively). When divided into two groups by the existence of cornea verticillata, there was a statistically significant difference in the anterior layer, 6–10-mm zone (p = 0.031); in the central layer, 0–2 mm (p = 0.012), 2–6 mm (p = 0.001), 6–10 mm (p = 0.002), and total (p = 0.002); and in the posterior layer, 6–10 mm (p = 0.004) and total (p = 0.002). Conclusions FD patients show higher corneal densitometry, and corneal densitometry may have potential for early diagnosis and reminding progress of FD.

Morbus Fabry

Morbus Fabry ist eine seltene, X-chromosomal vererbte lysosomale Speichererkrankung, die durch eine verminderte oder fehlende Aktivität des Enzyms α-Galaktosidase A bedingt ist 1, 2. Dadurch kommt es zu einer schleichenden Akkumulation von Glykosphingolipiden, v. a. Globotriaosylceramid (Gb3/GL3). Klinisch ist die Erkrankung durch eine Herzbeteiligung, eine zunehmende Niereninsuffizienz, Schlaganfälle, neuropathische, brennende Schmerzen an Händen und Füßen (Akroparästhesien), Angiokeratome der Haut und Hornhauteinlagerungen (Cornea verticillata) gekennzeichnet. Da die Symptome des M. Fabry meist unspezifisch sind, ist der Zeitraum bis zur Diagnose oft lang. Aufgrund des Erbgangs sind Männer meist stärker betroffen, bei Frauen ist das Bild variabler – sie können aber auch ähnlich schwere Symptome aufweisen.

Variables Associated with Glomerular Hyperfiltration in Fabry Disease Patients

Background: Fabry disease is a genetic disorder caused by the deficiency of the lysosomal α-galactosidase A enzyme. This failure generates the storage of globotriaosylceramide in different cells with a progressive multi-organ involvement. Objectives: To report the prevalence of glomerular hyperfiltration in Fabry disease patients and the association with clinical variables. Methods: Adult patients (≥ 18 years) at the moment of FD diagnosis were evaluated. The variables studied were: central and peripheral nervous system compromise, presence of arterial hypertension, cardiac arrhythmia, left ventricular hypertrophy, albuminuria/proteinuria, cornea verticillata, gastrointestinal involvement, treatment with inhibitors of the renin-angiotensin-aldosterone system, deafness, and presence of angiokeratomas. Results: Forty-eight adults with Fabry disease (35.9 ± 11.7 years), 28 women (58.3%), and 20 men (41.7%) were analyzed. Nine (18.8%) patients with glomerular hyperfiltration, including six females and three males (mean age: 28.8 years), were detected. A significant association between and central nervous system (P = 0.021) and peripheral nervous system (P = 0.001) compromise, cardiac arrhythmia (P = 0.001), cornea verticillata (P = 0.009), and gastrointestinal involvement (P = 0.009) was observed. However, no association was found between glomerular hyperfiltration and proteinuria or treatment with inhibitors of the renin-angiotensin-aldosterone system. Conclusions: This research showed a higher prevalence of glomerular hyperfiltration in the younger group and a significant association between glomerular hyperfiltration and some typical manifestations of classic Fabry patients. Although more studies are needed, it is concluded that other mechanisms than glomerular hyperfiltration, like injury by glycosphingolipids deposit into the filtration barrier, might influence the protein loss in Fabry nephropathy.

Ocular signs in Fabry Disease

Fabry disease is a rare, hereditary disease characterized by a deficiency of an enzyme, α galactosidase A (α gal A), responsible for progressive damage to many organs, leading to various symptomsn, Ocular damage, particularly to the cornea, is sometimes a precious element helping the positive diagnosis of the disease.We report the case of a 40-year-old patient diagnosed with Fabry disease, with bilateral conjunctival vascular toruosities , a "cornea verticillata and a peripheral cortical cataract. Better knowledge of ophthalmological signs, allows better screening and can participate in the evaluation of the effectiveness of substitute therapy. Keywords: α galactosidase A, cornea verticillata, hereditary, Farby disease

Fabry disease due to G171S GLA mutation: An atypical small nerve fiber sparing variant?

Introduction: To describe the ocular manifestations and in vivo confocal microscopic findings in a patient carrying the recently described hemizygous G171S GLA gene mutation. Case description: A 63-year-old Albanian male patient was evaluated for cataract surgery. Anamnesis showed pacemaker implantation in left ventricular hypertrophy, chronic kidney disease, family history for kidney transplantation, and late onset of sporadic acroparesthesias. Bilateral cornea verticillata, and increased tortuosity in conjunctival and retinal vessels were present. In vivo confocal microscopy revealed clusters of hyper-reflective corneal epithelial cells centripetally extending from the limbus. Interestingly, the nerve fiber number, density, and length in the corneal sub-basal nerve plexus were preserved. Alpha-galactosidase A activity was almost absent and hemizygous c.511G>A mutation (G171S – p.Gly171Ser) of the GLA gene was identified. The patient was referred for initiation of enzyme replacement therapy, and genetic counseling was recommended for at-risk family members. Conclusion: This is the third reported case of Fabry disease due to GLA G171S mutation. All patients are of Albanian descent. Cornea verticillata and vascular anomalies remain common ocular manifestations, as well as cardiac and renal involvement. Confirming its pathogenicity, this mutation results in a “classic” Fabry disease phenotype, but it seems to be associated with a relative small nerve fiber sparing that may delay a correct diagnosis. The diagnosis of Fabry disease still remains challenging due to its clinical heterogeneity, but a thorough ophthalmological examination can promote early detection and, consequently, early initiation of enzyme replacement therapy.