Ocular findings in patients with acquired ATTRv amyloidosis following domino liver transplantation.

PURPOSE: To investigate the presence of amyloidosis-related ocular findings in patients who received domino liver transplantation from ATTRv amyloidosis donors. METHODS: We reviewed the ocular findings in patients who had previously undergone domino liver transplantation and received ophthalmologic examinations between January 2009 and March 2023. The presence of amyloidosis-related ocular findings was retrospectively assessed by two ophthalmologists. RESULTS: During the study period, a total of 7 patients with 14 eyes were examined. All patients were considered as acquired ATTRv amyloidosis. The mean age at the final visit was 64.6±8.4 years (52-75 years), and the mean time since domino liver transplantation was 167.6±76.2 months (69-257 months). The two evaluators' assessments for amyloidosis-related ocular findings were completely identical. No amyloid fibril deposition was observed in the pupil, lens, or vitreous. Five patients (10 eyes) had a Schirmer test result of 5mm or less than 5 mm, and four patients with a total of 8 eyes underwent fluorescein angiography and indocyanine green angiography, and no evidence of retinal amyloid angiopathy was found on fluorescein angiography. However, three patients with 6 eyes showed choroidal amyloid angiopathy on indocyanine green angiography. CONCLUSION: While cases of choroidal amyloid angiopathy were observed, serious amyloidosis-related ocular complications such as vitreous opacity or secondary glaucoma did not occur even in the long term after domino liver transplantation.

Long-term surgical results of trabeculectomy for secondary glaucoma in Val30Met hereditary transthyretin amyloidosis.

This study reports the long-term results of trabeculectomy (LEC) for secondary glaucoma in hereditary transthyretin (ATTRv) amyloidosis patients and its correlation with prior vitrectomy. A retrospective case series was conducted involving 31 consecutive eyes of 20 ATTRv amyloidosis patients who underwent LEC between 2007 and 2020. The mean follow-up period was 73.2 ± 37.0 months (range: 20-181 months). Postoperative intraocular pressures (IOPs) were evaluated based on the following criteria: (a) IOP between 6 and 21 mmHg without additional glaucoma surgeries, except for laser suture lysis, (b) IOP between 6 and 15 mmHg without additional glaucoma surgeries, except for laser suture lysis, and (c) IOP between 6 and 21 mmHg without additional glaucoma surgeries, except for needling and laser suture lysis. Kaplan-Meier analysis revealed survival rates after LEC of 0.52 at 36 months, 0.42 at 60 months, and 0.25 at 84 months under criterion (a); 0.49 at 36 months, 0.27 at 60 months, and 0.11 at 84 months under criterion (b); and 0.76 at 36 months, 0.71 at 60 months, and 0.65 at 84 months under criterion (c). Eyes with a history of small gauge transconjunctival vitrectomy (SGTV) exhibited a tendency towards lower survival rates, although no statistically significant difference was observed (log-rank test; p = 0.193 under criterion (a) and p = 0.0553 under criterion (b)). Our findings suggest that LEC and additional needling procedures can provide some control over IOP; however, the overall postoperative outcomes of LEC for ATTRv amyloidosis remain unsatisfactory, even in the era of SGTV with reduced conjunctival scarring.

Microhook ab interno trabeculotomy for secondary glaucoma in patients with hereditary transthyretin amyloidosis.

PURPOSE: To report surgical outcomes of a Microhook ab interno trabeculotomy (µLOT) procedure for glaucoma secondary to hereditary transthyretin amyloidosis (ATTRv). STUDY DESIGN: Retrospective case series. METHODS: Medical records of patients with glaucoma secondary to ATTRv with transthyretin Val30Met variant, who underwent µLOT, were retrospectively reviewed. Surgical success was categorized according to the postoperative intraocular pressures (IOPs, mmHg) as follows: (a) 6 ≤ IOP ≤ 21; (b) 6 ≤ IOP ≤ 18; and (c) 6 ≤ IOP ≤ 15, without light perception loss or additional glaucoma surgery. Secondary outcomes were glaucoma medication scores and postoperative complications. RESULTS: This study included 18 eyes (13 patients, 6 men). The mean follow-up period was 25.2±9.8 months (7-38 months). Kaplan-Meier analysis indicated success rates of (a) 1.00 at 6, 1.00 at 12, and 0.43 at 24 months; (b), 1.00 at 6, 0.93 at 12, and 0.43 at 24 months; (c) 0.94 at 6, 0.75 at 12, and 0.27 at 24 months after operation. Postoperative IOPs were significantly reduced from the baseline of 25.2±5.8 mmHg to 11.5±2.7 at 3, 12.3±4.1 at 6, and 13.8±3.9 at 12 months (Dunnett's test). Medication scores were also improved at 3 and 6 months but without a significant reduction at 12 months. There were no severe complications requiring surgical intervention except for additional glaucoma surgery. CONCLUSION: µLOT for secondary glaucoma in ATTRv is safe and effective 1 year after surgery, but the effects diminish after 2 years.

Application of optical coherence tomography angiography to assess systemic severity in patients with hereditary transthyretin amyloidosis.

Hereditary transthyretin amyloidosis is an autosomal dominant form of amyloidosis caused by an abnormality in transthyretin, with various ocular manifestations. Among these, ocular amyloid angiopathy has attracted attention because of its direct link to visual impairment and its correlation with systemic severity. We hypothesized that optical coherence tomography angiographic parameters would be useful biomarkers of amyloidosis systemic severity and investigated their correlation with the systemic severity score. The primary outcome was the correlation between the systemic severity score and choriocapillaris flow deficit percentage. Secondary outcomes were the correlations between the systemic severity score and retinal optical coherence tomography angiographic parameters, including foveal avascular zone size and circularity and superficial/deep/total retinal perfusion and vessel densities. The choroidal and retinal vasculature was quantified in 36 eyes from 36 patients (age, 51.8±12.1 years; disease duration, 13.4±6.2 years). Ten eyes had a history of vitrectomy for vitreous opacity. Choriocapillaris flow deficit percentage was not significantly correlated with the systemic severity score (Spearman's rank correlation: r = 2.96×10-2, p = 0.863). Similarly, foveal avascular zone size and circularity, and superficial/deep/total retinal perfusion and vessel densities were not significantly correlated with the systemic severity score. These results may indicate that optical coherence tomography angiographic parameters are not sufficient to predict amyloidosis severity.

OCULAR ANGIOGRAPHIC FEATURES IN JAPANESE PATIENTS WITH VAL30MET HEREDITARY TRANSTHYRETIN AMYLOIDOSIS.

PURPOSE: To investigate ocular angiographic features of hereditary transthyretin amyloidosis with transthyretin Val30Met mutation (hATTR-V30M) in Japanese patients. METHODS: We retrospectively reviewed 102 eyes of 51 patients with hATTR-V30M who underwent fluorescein angiograms and indocyanine green angiograms between 2012 and 2018. Systemic severity score, fluorescein angiograms, indocyanine green angiograms, and ocular amyloidosis presentations at the final angiograms and subsequent neovascular events were evaluated. Primary outcomes were the frequency of choroidal amyloid angiopathy and retinal amyloid angiopathy (RAA). Secondary outcomes were their correlations to the systemic severity score. RESULTS: Six eyes could not be evaluated by fluorescein angiogram because of vitreous opacity. Of 96 eyes evaluated, RAA was detected in 36 (37.5%). Neovascularization was not detected. Indocyanine green angiogram indicated choroidal amyloid angiopathy in 46/51 patients (90.2%), with distinct patterns-diffuse (n = 6), focal (n = 14), and punctiform (n = 26)-based on late-phase hypercyanescence. Retinal amyloid angiopathy and choroidal amyloid angiopathy grades were associated with systemic severity (ρ = 0.57 and 0.50, respectively; both P < 0.05). At 35.4 ± 28.4 (0-96) months, iris-rubeosis was observed in one eye and vitreous hemorrhage in two. CONCLUSION: Retinal amyloid angiopathy was less common and choroidal amyloid angiopathy was frequent, and their severity correlated with the systemic severity score. The frequencies of RAA and subsequent neovascular events in this study may suggest regional differences in the ocular angiographic features of hATTR-V30M.

Complete regression of branching vascular network in polypoidal choroidal vasculopathy by ranibizumab and photodynamic therapy, two case reports.

BACKGROUND: Polypoidal choroidal vasculopathy (PCV) consists of polyps that potentially cause massive subretinal hemorrhage and their branching vascular network (BVN) of feeder vessels. Although conventional indocyanine green angiography (IA) has shown anti-vascular endothelial growth factor (VEGF) agents and/or photodynamic therapy (PDT) to successfully induce polyp closure, the BVN appears resistant to these therapies and serves as the origin of recurrent active polyps. Recently introduced optical coherence tomography angiography (OCT-A) enables more frequent angiographic evaluation of polyps and the BVN than does conventional IA since it does not require intravenous fluorescent dye injection and is thus considered non-invasive. CASE PRESENTATION: Case 1. A 70-year-old male with PCV in his left eye suffered from vision deterioration (20/40) due to persistent subretinal fluid despite 42 intravitreal injections of ranibizumab (IVRs) over 5 years and 7 months. PDT was performed as an adjunct therapy 3 days after the 43rd IVR. IA at 3 months after PDT showed successful polyp closure but persisting BVN. However, more frequent evaluation with OCT-A starting at 1 week after PDT demonstrated complete regression of both the BVN and polyp. OCT-A at every subsequent outpatient visit depicted gradual re-perfusion of the BVN and the restoration of most of its original network at 3 months, which was compatible with IA findings. Neither OCTA nor IA revealed polyp recurrence at 3 months. Case 2. A 65-year-old female suffering from left vision deterioration due to PCV underwent 5 intravitreal injections of aflibercept. Since her subretinal fluid persisted, the treatment was switched to a combination of IVR and PDT. OCT-A revealed marked regression of the BVN and polyp at 2 weeks, but the BVN had regained its original shape at 2 months without any sign of polyp recurrence. CONCLUSIONS: Differently from previous observations obtained by IA alone, more frequent non-invasive OCT-A examination revealed complete but transient regression of the BVN just after combination therapy with IVR and PDT.