Hereditary transthyretin amyloidosis (hATTR) is a rare disease caused by a point mutation in the transthyretin (TTR) gene and inherited in an autosomal dominant fashion. TTR is a plasma protein that functions as a carrier for thyroxine (T4) and retinol (vitamin A). Ophthalmological manifestations are due to both the hepatic and ocular production of mutated TTR. In this case series, we report the ocular manifestations of hATTR in eighteen eyes of nine consecutive patients. Corneal nerve abnormalities as well as morphological and functional changes in the retina were investigated. The study was a single-center, retrospective, observational, clinical case series. In all patients, corneal confocal microscopy (CCM), multimodal imaging of the retina, including fundus photography and Optical Coherence Tomography (OCT), as well as rod and cone electroretinography (ERG) were performed. Eight patients had active disease and one was an unaffected carrier. In all study eyes, corneal nerve plexa examined with CCM were poorly represented or absent. Mixed rod-cone and cone ERG b-wave amplitudes were reduced, and photopic b-wave responses were significantly delayed. Photopic Negative Response (PhNR) amplitude was significantly reduced, while PhNR latency was significantly augmented. In 13/18 eyes, vitreous opacities and abnormalities of vitreo-retinal interface were found. The current results highlight the presence of corneal nerve damage. Functional retinal abnormalities, detected by ERG, can be found even in the presence of minimal or absent structural retinal damage. These findings support the use of CCM and ERGs to detect early biomarkers for primary hATTR.

The present study aimed to investigate ocular findings in hereditary transthyretin amyloidosis (ATTRv) pre-symptomatic carriers. Fourteen ATTRv pre-symptomatic carriers, who are patients with positive genetic testing but without signs or symptoms of the disease, were retrospectively evaluated. Retinal morphology was assessed using optical coherence tomography (OCT) and OCT-angiography. Retinal function was evaluated using cone b-wave and photopic negative response (PhNR). Pupillometry and in vivo corneal confocal microscopy (IVCM) were performed. ATTRv pre-symptomatic carriers presented a significantly reduced central macular thickness (CMT) (p = 0.01) and outer nuclear layer (ONL) thickness (p = 0.01) in comparison to normal controls. No differences were found when analyzing sub-foveal choroidal thickness, retinal nerve fiber layer and ganglion cell complex. In comparison to healthy controls, pre-symptomatic carriers presented an attenuated superficial retinal vascular network and a significantly augmented PhNR amplitude (p = 0.01). However, PhNR implicit times, B-wave amplitude and B-wave peak time did not show significant differences in comparison to controls. No differences were found for pupillometric values. All the examined eyes presented alterations in the IVCM. Preclinical ocular structural and functional abnormalities can be found in ATTRv pre-symptomatic carriers. Thus, an extensive ophthalmological evaluation should be included at the baseline visit and during follow-up. Considering the availability of new drugs potentially able to prevent or delay disease progression, the identification of new disease biomarkers appears to be particularly promising.

Background: Mirvetuximab soravtansine (MIRV) improves outcomes in FRα-positive, platinum-resistant ovarian cancer; however ocular adverse events (OAEs), particularly corneal epithelial toxicity, are frequent and warrant structured ophthalmologic monitoring. Methods: In this retrospective observational study, 31 consecutive patients receiving MIRV for FRα-positive gynecologic malignancies underwent standardized ophthalmic assessments at baseline and prior to each treatment cycle (every 21 days). The protocol included best corrected visual acuity (BCVA), slit-lamp biomicroscopy, anterior-segment optical coherence tomography (AS-OCT), corneal topography, and tear film analysis. OAEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0, based on symptom severity and functional impairment. Results: OAEs occurred in all patients (31/31, 100%), predominantly grade 1–2. Corneal epithelial toxicity was documented in 28/31 patients (90.3%), while no grade ≥ 3 events were observed. Symptoms typically developed 7–14 days after the second infusion. AS-OCT and corneal topography consistently revealed epithelial microcysts and surface irregularities, which were usually detected during scheduled pre-cycle ophthalmologic evaluations. Tear-film instability (break-up time ≤ 5 s) developed in 19/31 patients (61.3%), generally within 10 days after the second infusion, and improved in all but 2 patients (6.5%) following prophylactic lubrication. Transient refractive changes occurred in 28/31 patients (90.3%) and were associated with a temporary BCVA reduction (mean nadir ~20/32 Snellen), followed by recovery during follow-up. Conclusions: MIRV-related ocular alterations are frequent but reversible and clinically manageable. Multimodal imaging combined with functional and refractive assessment provides sensitive markers of corneal epithelial toxicity and supports integrated ophthalmologic monitoring to preserve visual function and maintain oncologic treatment continuity.

Purpose: The purpose of this study was to evaluate and compare clinical and visual outcomes, complications, and endothelial cell survival of different endothelial keratoplasty (EK) techniques—Descemet membrane endothelial keratoplasty (DMEK), preloaded DMEK (PL-DMEK), ultra-thin Descemet stripping automated endothelial keratoplasty (UT-DSAEK), and standard DSAEK—using real-world multicenter data. Methods: This retrospective multicenter cohort study included patients undergoing EK across 11 corneal centers in Italy. Clinical and visual outcomes were collected at baseline, 3, 6, and 12 months, and at last follow-up. Donor graft characteristics and their impact on postoperative outcomes were analyzed. Results: A total of 969 eyes were included. All EK techniques resulted in significant improvement in best-corrected visual acuity (BCVA). Although DMEK and PL-DMEK achieved better final BCVA, these groups had better baseline BCVA, and no significant differences in absolute BCVA recovery were observed among techniques, except for greater improvement with UT-DSAEK compared with DSAEK ( P = 0.020). Rebubbling rates were significantly higher in DMEK and PL-DMEK (34.3% and 31.7%) than in UT-DSAEK and DSAEK (16.0% and 16.9%; P < 0.05). Endothelial cell density loss was greater in DSAEK (57.8%) and UT-DSAEK (53.8%) compared with DMEK (46.8%) and PL-DMEK (42.3%) ( P < 0.001). Rejection rates did not differ significantly. Preservation media significantly influenced storage duration, BCVA, and pachymetry in analyses adjusted for baseline (ANCOVA P < 0.001), with Eusol, E-MEM + 6% dextran, and Tissue-C showing the most favorable outcomes. Conclusions: In this large multicenter real-world cohort, all EK techniques provided significant clinical benefit. Differences in visual outcomes, endothelial cell survival, and complication profiles support an individualized approach based on patient, donor, and surgical factors.