CHOROIDAL INVOLVEMENT IN HEREDITARY TRANSTHYRETIN AMYLOIDOSIS PATIENTS.

PURPOSE: To compare the choroidal characteristics between the eyes of patients with and without hereditary transthyretin amyloidosis. METHODS: Case-control observational study with choroidal thickness and vasculature evaluation by optical coherence tomography with enhanced depth imaging protocol of the macula. RESULTS: The study included 332 eyes: 166 eyes of hereditary transthyretin amyloidosis patients and 166 eyes of healthy patients. Mean age was similar between groups (P = 0.979). For hereditary transthyretin amyloidosis patients, on average, in all sectors analyzed (in the full 5 mm-width image [G] and also in 1-mm-width central [C], nasal [N], and temporal [T] sectors), there was a higher stromal area, a lower choroidal thickness, and a lower choroidal vascularity index, compared with the control group. The linear mixed models revealed no differences according to the systemic treatment groups. CONCLUSION: Hereditary transthyretin amyloidosis patients showed statistically significant differences in choroidal characteristics, compared with eyes without pathology. These age-related and statistically significant changes compared with the healthy eyes may help in the future to better monitor the systemic hereditary transthyretin amyloidosis disease and complement other systemic evaluations, including on clinical trials to analyze more objectively, the results of new therapies.

Changes in Ganglion Cell Layer Thickness after Treatment with the 0.2 µg/day Fluocinolone Acetonide Implant in Vitrectomized and Nonvitrectomized Eyes with Diabetic Macular Edema.

INTRODUCTION: The objective of this study is to compare changes in ganglion cell layer (GCL) between vitrectomized and nonvitrectomized eyes with diabetic macular edema (DME) over a 2-year period following treatment with 0.2 µg/day fluocinolone acetonide (FAc) implant. METHODS: Eighteen vitrectomized (group 1) and 8 nonvitrectomized (group 2) eyes were included in this cohort study. Changes in central macula GCL thickness were measured using the Spectralis spectral domain-optical coherence tomography at baseline and 6, 12, and 24 months of follow-up. Other parameters analyzed included best-corrected visual acuity (BCVA), central foveal thickness (CFT), and intraocular pressure (IOP). RESULTS: Treatment with the FAc implant led to small reductions in mean global GCL thickness versus baseline and contrasts with the control group that was stable or slightly increased versus baseline. FAc therapy also led to improvements in mean BCVA and CFT that were observed at Month 6 and maintained to Month 24. For vitrectomized and nonvitrectomized eyes, no differences were observed between mean global GCL, BCVA, and CFT values during follow-up. Linear correlations revealed that in all groups mean BCVA at Month 24 positively correlated with mean GCL thickness at baseline and at Month 24. IOP remained stable throughout the 24 months. CONCLUSION: There was no evident retinal neurodegeneration in the 2-year period following treatment with FAc in both groups. GCL thickness may be a useful biomarker for assessing safety and effectiveness in patients with DME.

Epiretinal membrane vitrectomy: outcomes with or without cataract surgery and a novel prognostic factor for cystoid macular edema.

PURPOSE: To assess the outcomes of vitrectomy with or without cataract surgery for the treatment of idiopathic ERM in phakic eyes and evaluate predictors of functional and anatomical outcomes. METHODS: Retrospective cohort of consecutive phakic ERM eyes distributed in three groups: a) combined (phacovitrectomy) group, b) PPV-only group, and c) consecutive group (PPV followed by cataract surgery). Main outcomes were final visual acuity (VA) and cystoid macular edema (CME) occurrence. Potential predictors of VA or CME included clinical variables and SD-OCT parameters. RESULTS: A total of 108 eyes were included in this study. There were no differences in the final VA between consecutive and combined groups (0.22 vs 0.10 logMAR, p = 0.851). Twelve eyes from the combined group (23%) and one eye from the PPV-only group presented CME (p = 0.001). There were no differences between postoperative CME occurrence in combined versus consecutive group (12 vs 7, p = 0.38). The presence of cotton-ball sign predicted the development of CME [OR 2.86 (95%CI 1.01-8.18), p = 0.049] while separated ERM-ILM complex was found to be protective [OR 0.25 (95%CI 0.08-0.77), p = 0.015]. CONCLUSIONS: Functional and anatomical results of PPV with ERM and ILM peeling combined with cataract surgery was equivalent to the consecutive procedure, with both strategies being effective. Separated ERM-ILM complex has prognostic value in these patients, as its presence at baseline was found to be protective for postoperative CME.

Optical Coherence Tomography Biomarkers: Vitreous Status Influence in Outcomes for Diabetic Macular Edema Therapy with 0.19-mg Fluocinolone Acetonide Implant.

BACKGROUND: The 0.19-mg fluocinolone acetonide (FAc) implant (ILUVIEN®; Alimera Sciences Ltd., Hampshire, UK) was approved for the treatment of vision impairment associated with chronic and refractory diabetic macular edema (DME). OBJECTIVES: To quantitatively assess functional and structural features in nonvitrectomized and vitrectomized DME patients after being treated with an FAc implant. METHODS: Retrospective review of patients with DME receiving a single intravitreal injection of the FAc implant. The study was designed to analyze the presence of quantitative structural OCT biomarkers at baseline and 12 months after FAc therapy according to vitreous status. RESULTS: A total of 41 eyes from 30 patients were included in this study. At 12 months after injection, vitrectomized patients had a lower central foveal thickness (p = 0.017) and fewer hyperreflective dots (p = 0.028) compared with nonvitrectomized. Thirty (73%) patients presented a significant functional improvement with 17 (42%) increasing at least 15 ETDRS letters. Overall, 22 (54%) eyes had a complete resolution of DME at the 12-month visit. Patients who needed additional therapy had a higher prevalence of subretinal fluid (42 vs. 3%, p = 0.005) at baseline. CONCLUSIONS: This study supports the effectiveness of the FAc implant and reports significant changes at 12 months after FAc injection.

Inverted internal limiting membrane flap technique in the surgical treatment of macular holes: 8-year experience.

PURPOSE: To evaluate the ellipsoid zone (EZ) structural recovery, hole closure rate, and visual acuity improvement after inverted internal limiting membrane (ILM) flap technique. METHODS: Retrospective cohort of eyes affected by idiopathic macular holes (MH) that underwent pars plana vitrectomy combined with inverted ILM flap technique in a tertiary center, over an 8-year period (2011-2019). The main outcomes were the postoperative qualitative analysis of EZ structure on spectral-domain optical coherence tomography, hole closure rate, and best-corrected visual acuity (BCVA) improvement of ≥ 0.3 units in the logarithm of minimal angle of resolution (logMAR) scale. RESULTS: Our study included 76 eyes of 72 patients; 65% were female, with a mean age of 70 ± 8 years-old. Median (range) follow-up was 21 (3-92) months. Hole closure rate was 92%. Structural defects in EZ were observed in 66% of closed holes (EZ atrophy in 33%, EZ disruption in 22%, and EZ thinning in 11%). The mean final BCVA was 0.5 ± 0.4 logMAR (Snellen 20/63), but visual acuity improvement occurred in 80% of the eyes. Final BCVA was significantly worse in eyes with EZ atrophy compared with eyes with EZ disruption (0.75 vs. 0.36 logMAR, p = 0.004) and EZ thinning (0.75 vs. 0.32 logMAR, p = 0.015). In multivariate regression, minimum linear diameter (OR 1.01; IC 95% 1.01-1.02) independently predicted a final BCVA (logMAR) < 0.3 units. CONCLUSION: Inverted ILM flap technique provided a hole closure rate above 90%, similar to previous studies. Although the modest value of the final BCVA, a significant visual acuity improvement occurred in most eyes. Structural defects of EZ were found in more than half of closed MHs after surgery. Evidence of postoperative retinal atrophy was associated with a worse visual outcome.

Avoiding misdiagnosis: expert consensus recommendations for the suspicion and diagnosis of transthyretin amyloidosis for the general practitioner.

BACKGROUND: Transthyretin amyloidosis (also known as ATTR amyloidosis) is a systemic, life-threatening disease characterized by transthyretin (TTR) fibril deposition in organs and tissue. A definitive diagnosis of ATTR amyloidosis is often a challenge, in large part because of its heterogeneous presentation. Although ATTR amyloidosis was previously considered untreatable, disease-modifying therapies for the treatment of this disease have recently become available. This article aims to raise awareness of the initial symptoms of ATTR amyloidosis among general practitioners to facilitate identification of a patient with suspicious signs and symptoms. METHODS: These consensus recommendations for the suspicion and diagnosis of ATTR amyloidosis were developed through a series of development and review cycles by an international working group comprising key amyloidosis specialists. This working group met to discuss the barriers to early and accurate diagnosis of ATTR amyloidosis and develop a consensus recommendation through a thorough search of the literature performed using PubMed Central. RESULTS: The cardiac and peripheral nervous systems are most frequently involved in ATTR amyloidosis; however, many patients often also experience gastrointestinal and other systemic manifestations. Given the multisystemic nature of symptoms, ATTR amyloidosis is often misdiagnosed as a more common disorder, leading to significant delays in the initiation of treatment. Although histologic evaluation has been the gold standard to confirm ATTR amyloidosis, a range of tools are available that can facilitate early and accurate diagnosis. Of importance, genetic testing should be considered early in the evaluation of a patient with unexplained peripheral neuropathy. CONCLUSIONS: A diagnostic algorithm based on initial red flag symptoms and manifestations of cardiac or neurologic involvement will facilitate identification by the general practitioner of a patient with clinically suspicious symptoms, enabling subsequent referral of the patient to a multidisciplinary specialized medical center.

Intraocular lens power calculation: angle κ and ocular biomechanics.

PURPOSE: To study the effect of ocular biomechanics on the prediction error of intraocular lens (IOL) power calculation. SETTING: Centro Hospitalar Universitário do Porto, Porto, Portugal. DESIGN: Prospective longitudinal study. METHODS: This study included 67 subjects. Before cataract surgery subjects underwent biometry with IOLMaster 700 and biomechanical analysis with Corvis Scheimpflug technology. The targeted spherical equivalent was calculated with SRK-T and Barrett Universal II. Associations between prediction error (PE), absolute prediction error (AE), and biometric and biomechanical parameters were performed with stepwise multivariate linear correlation analysis. RESULTS: Using the SRKT formula, there was association between PE and Corvis Biomechanical Index (CBI, B = -0.531, P = .011) and between AE and the horizontal offset between the center of the pupil and the visual axis (angle κ, B = -0.274, P = .007). Considering the Barret Universal II formula, PE was independently associated with anterior chamber depth ( B = -0.279, P = .021) and CBI ( B = -0.520, P = .013) and AE was associated with angle κ ( B = -0.370, P = .007). CONCLUSIONS: A large angle κ may reduce the predictability of IOL power calculation. Ocular biomechanics likely influence the refractive outcomes after IOL implantation. This study showed that eyes with softer corneal biomechanics had more myopic PE. This may relate to anteriorization of the effective lens position. Dynamic measurements may be the way to progress into future formulas.

Oct biomarkers for early prognosis in diabetic macular edema treatment with ranibizumab.

BACKGROUND: Diabetic macular edema is the main cause of vision loss in patients with diabetic retinopathy. In this work, we aimed to assess the role of Optical Coherence Tomography (OCT) biomarkers in patients treated with ranibizumab. METHODS: A prospective study enrolling 46 eyes with DME under ranibizumab intravitreal therapy with 12 months of follow-up. The primary endpoint was to assess the association between OCT biomarkers at baseline and the type of treatment response. RESULTS: Good responders, compared with partial/non responders, had lower number of inner nuclear layer cysts (INLc) at baseline, (26.5% vs 73.5%, p = 0.035) and presented, at 12 months of follow-up, lower percentage of disorganization of retinal inner layers (12.0% vs 88.0%, p = 0.001), lower disruption of outer plexiform layer (8.7% vs 91.3%, p < 0.001) and lower outer nuclear layer cysts (17.4% vs 82.6%, p = 0.013). At the end of follow-up, it was observed a higher frequency of inner nuclear layer cysts in patients with higher glycated haemoglobin (p = 0.028). CONCLUSION: This study showed the value and importance of OCT parameters, such as absence of INLc, as a prognostic therapeutic response. A normalization of the macular anatomy with ranibizumab is more likely to happen in early complete responders. The association between INLc and higher glycated haemoglobin levels showed the importance of systemic metabolic control in systemic diabetic manifestations. Clinicaltrials.gov NCT04387604.

Pupillometry: An objective test to assess endocular hereditary transthyretin amyloidosis.

OBJECTIVE: To automatically study the pupillary light reflex in patients with hereditary transthyretin-associated amyloidosis (hATTR). METHODS: Prospective cross-sectional observational study in patients with hATTR with unilateral scalloped iris. Pupillary light reflex of scalloped iris eyes (21 eyes) were compared with non-scalloped iris eyes (21 eyes, paired eyes of the same patients) and also with a control group of 20 healthy eyes, using static and dynamic pupillometry with the Metrovision® MonPack One. RESULTS: No patient presented evident neurological involvment of the cranial nerves. No significant differences were found in the pupillary diameters under standardized lighting conditions (static pupillometry) among groups. In dynamic pupillometry, the amplitude of contraction, the velocity of contraction and the velocity of dilation were statistically significantly lower in eyes with scalloped iris, comparing both with the contralateral non-scalloped iris eyes (p < 0.001 for all) and with eyes from healthy subjects (p < 0.05 for all). CONCLUSION: A scalloped iris reflects a more advanced endocular hATTR and it is associated with an altered pupillary light reflex. Pupillometry may be a quick, simple, and portable test to objectively evaluate ocular amyloid deposition in hATTR eyes. Pupillary light reflex may not be reliable to evaluate neurological dysfunction in these patients.

Ahmed valve for secondary glaucoma in patients with hereditary transthyretin amyloidosis.

OBJECTIVE: To evaluate the surgical outcomes of patients with hereditary transthyretin amyloidosis (TTR-FAP) who underwent Ahmed glaucoma valve (AGV) implantation. METHODS: A retrospective cohort study was performed on patients with a diagnosis of TTR-FAP secondary glaucoma, who underwent AGV implantation in our department, between November 2010 and July 2019. The cumulative probability of treatment success was measured with Kaplan-Meier survival analysis. The primary outcome was success, defined as intraocular pressure (IOP) ≥ 6 mmHg and ≤21 mmHg with or without medication, with no need for further glaucoma surgery and without loss of light perception at last follow-up. Secondary outcomes were postoperative IOP, number of IOP-lowering medications, and rates of complications. RESULTS: The study included 114 eyes of 87 patients. The mean follow-up duration was 3.81 ± 2.11 years (y) [range, 1.00-8.28 y]. Compared to the preoperative values, the mean IOP was reduced from 28.20 ± 7.01 to 12.87 ± 3.76 mmHg at the final visit (p < 0.001), with a reduction in the number of medications from 3.89 ± 0.66 to 1.86 ± 1.43 (p < 0.001). Early and late postoperative complications occurred in 20 (17.09%) and 9 (7.89%) eyes, respectively. Kaplan-Meier analysis indicated probabilities of success of 0.98 at 1 y, 0.97 at 2 y, 0.95 at 3 y, 0.89 at 4 y, 0.77 at 5 y and 0.72 at 6 y. The linear correlation analysis showed a correlation between some characteristics of the natural history of TTR-FAP patients and AGV implantation success. CONCLUSION: Although glaucoma in TTR-FAP patients is very difficult to manage, AGV implantation is an effective and relatively safe procedure.

Corneal Biomechanical Assessment with Ultra-High-Speed Scheimpflug Imaging During Non-Contact Tonometry: A Prospective Review.

BACKGROUND: In recent years, increasing interest has arisen in the application of data from corneal biomechanics in many areas of ophthalmology, particularly to assist in the detection of early corneal ectasia or ectasia susceptibility, to predict corneal response to surgical or therapeutic interventions and in glaucoma management. Technology has evolved and, recently, the Scheimpflug principle was associated with a non-contact air-puff tonometer, allowing a thorough analysis of corneal biomechanics and a biomechanically corrected intraocular pressure assessment, opening up new perspectives both in ophthalmology and in other medical areas. Data from corneal biomechanics assessment are being integrated in artificial intelligence models in order to increase its value in clinical practice. OBJECTIVE: To review the state of the art in the field of corneal biomechanics assessment with special emphasis to the technology based on ultra-high-speed Scheimpflug imaging during non-contact tonometry. SUMMARY: A meticulous literature review was performed until the present day. We used 136 published manuscripts as our references. Both information from healthy individuals and descriptions of possible associations with systemic diseases are described. Additionally, it exposed information regarding several fields of ocular pathology, from cornea and ocular surface through areas of refractive surgery and glaucoma until vascular and structural diseases of the chorioretinal unit.

Subclinical retinal angiopathy associated with hereditary transthyretin amyloidosis - assessed with optical coherence tomography angiography.

BACKGROUND: Retinal angiopathy is a known ocular manifestation of hereditary transthyretin amyloidosis (ATTRv). Optical coherence tomography angiography (OCT-A) is a recent noninvasive imaging technique, used in other retinal vascular diseases. Our purpose was to analyse subclinical changes in retinal vessels, with OCT-A, in patients with ATTRv amyloidosis. METHODS: Observational cross-sectional study in Centro Hospitalar e Universitário do Porto in the cohort of patients with genetic diagnosis of ATTRv. Patients were included if they had just one eye with scalloped iris (the other eye without scalloped iris), postulating eyes were at different stages, in the same patient. Patients were excluded if they had other manifestations of ocular ATTRv amyloidosis, namely clinical retinal angiopathy and/or vitreous opacities. The group of eyes with scalloped iris were compared with eyes without scalloped iris, using paired tests. Values are shown as Δ = mean difference between groups; p = p-value, d = Cohen's d for effect size measurement. RESULTS: Twenty-four patients (24 eyes in each group) were included. Mean age was 46.5 ± 5.0 years. Eyes with scalloped iris showed attenuated retinal vascular network: larger foveal avascular zone (FAZ) area (Δ = +0.02 mm2, p = 0.002, d = 0.70); decreased foveal vascular density (Δ = -3.57%, p = 0.001, d = -0.75); superficial (Δ = -1.50%, p = 0.049, d = -0.43) and deep (Δ = -2.53%, p = 0.023, d = -0.50) plexus vascular density. Acircularity index was superior in scalloped iris eyes (Δ = 0.04, p = 0.004, d = -0.65), representing an abnormal FAZ morphology. CONCLUSION: Scalloped iris in ATTRv eyes are associated with a more advanced subclinical retinal angiopathy, than eyes without scalloped iris. Our results identify for the first time and in vivo, early changes in retinal vessels in ATTRv amyloidosis. Henceforward, OCT-A may play a role in the evaluation of ATTRv patients oculopathy and the effectiveness of future eye targeting treatments.

Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy.

Amyloid transthyretin (ATTR) amyloidosis with polyneuropathy (PN) is a progressive, debilitating, systemic disease wherein transthyretin protein misfolds to form amyloid, which is deposited in the endoneurium. ATTR amyloidosis with PN is the most serious hereditary polyneuropathy of adult onset. It arises from a hereditary mutation in the TTR gene and may involve the heart as well as other organs. It is critical to identify and diagnose the disease earlier because treatments are available to help slow the progression of neuropathy. Early diagnosis is complicated, however, because presentation may vary and family history is not always known. Symptoms may be mistakenly attributed to other diseases such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), idiopathic axonal polyneuropathy, lumbar spinal stenosis, and, more rarely, diabetic neuropathy and AL amyloidosis. In endemic countries (e.g., Portugal, Japan, Sweden, Brazil), ATTR amyloidosis with PN should be suspected in any patient who has length-dependent small-fiber PN with autonomic dysfunction and a family history of ATTR amyloidosis, unexplained weight loss, heart rhythm disorders, vitreous opacities, or renal abnormalities. In nonendemic countries, the disease may present as idiopathic rapidly progressive sensory motor axonal neuropathy or atypical CIDP with any of the above symptoms or with bilateral carpal tunnel syndrome, gait disorders, or cardiac hypertrophy. Diagnosis should include DNA testing, biopsy, and amyloid typing. Patients should be followed up every 6-12 months, depending on the severity of the disease and response to therapy. This review outlines detailed recommendations to improve the diagnosis of ATTR amyloidosis with PN.

Oligomeric TTR V30M aggregates compromise cell viability, erythropoietin gene expression and promoter activity in the human hepatoma cell line Hep3B.

Familial amyloidotic polyneuropathy, ATTRV30M (p. TTRV50M) amyloidosis, is a neurodegenerative disease characterized by systemic extracellular amyloid deposition of a mutant transthyretin, TTR V30M. Anemia, with low erythropoietin (EPO) levels and spared kidney function, affects about 25% of symptomatic patients, suggesting a blockage of EPO-producing cells. Early non-fibrillar TTR aggregates are highly cytotoxic, inducing oxidative stress, the expression of apoptosis-related molecules and secretion of pro-inflammatory cytokines, factors capable of inhibiting EPO production. Low EPO levels in these patients are not related to renal amyloid deposition or the presence of circulating TTR V30M. However, the role of early non-fibrillar TTR aggregates remains unexplored. We used the EPO producing Hep3B human hepatoma cell line to study the effect of TTR oligomeric aggregates on EPO expression. Hep3B cells were incubated with soluble and oligomeric TTR V30M, and cell proliferation as well as caspase 3/7 activation was evaluated. Relative quantification of EPO mRNA transcripts was performed by real-time PCR. Significant reductions in cell viability (13 ± 7.3%) and activation of caspases 3/7 were seen after 24 h in the presence of oligomeric TTR V30M. Also, EPO expression was significantly reduced (50 ± 2.8%), in normoxic conditions. A reporter assay was constructed with a PCR fragment of the EPO promoter linked to the luciferase gene to evaluate the role of transcription factors targeting the promoter. A significant reduction of EPO promoter activity (53 ± 6.5%) was observed in transfected cells exposed to TTR oligomers. Our results show that oligomeric TTR V30M reduces EPO expression, at least in part through inhibition of promoter activity.

Ophthalmological manifestations in hereditary transthyretin (ATTR V30M) carriers: a review of 513 cases.

PURPOSE: Assessment of ocular involvement in transthyretin-related familial amyloidosis with polyneuropathy (FAP) in a large cohort of Portuguese patients. METHODS: We reviewed the medical records of 513 Portuguese FAP mutation carriers, at the Ophthalmology Service, Centro Hospitalar do Porto, between 1 January 2008 and 31 January 2013. Abnormal conjunctiva vessels (ACV), Schirmer test, tear break-up time (TBUT), amyloid deposition on the iris (DAI), scalloped iris, amyloid deposition on the anterior capsule of the lens (DAL), vitreous amyloidosis, retinal amyloid angiopathy and glaucoma were evaluated and registered. RESULTS: Of the 513 carriers, 477 (93%) had clinical systemic disease with a median duration of 9.3 (5.1-13.7) years and 247 were men. Of these, 343 (72%) had been liver transplanted, on median of 6.6 (3.3-10.8) years before inclusion in this study. No ocular abnormalities were identified in the asymptomatic carriers (7%). The abnormalities observed with decreasing frequency were abnormal TBUT (379 patients, 79.5%, 751 eyes), abnormal Schirmer test (320 patients, 67%, 635 eyes), DAI (183 patients, 38.4%, 350 eyes), DAL (157 patients, 32.9%, 308 eyes), scalloped iris (133 patients, 27.9%, 238 eyes), glaucoma (97 patients, 20%, 165 eyes), vitreous amyloidosis (83 patients, 17.4%, 139 eyes), ACV (68 patients, 14%, 136 eyes) and amyloidotic retinal angiopathy (21 patients, 4%, 32 eyes). Patients with abnormal Schirmer test (p < 0.001), scalloped iris (p = 0.006) and vitreous amyloidosis (p = 0.007) were significantly older than the others. According to their age of onset of systemic disease, the patients have been split into early-onset (<40 years old), intermediate-onset (40-50 years old), late onset (>50 years old) and asymptomatic carriers. We observed a statistically significant difference in the prevalence of ACV (p = 0.045) and of an abnormal Schirmer test (p = 0.004) between groups. Transplanted patients have a significantly higher prevalence of DAI (p = 0.001), DAL (p = 0.009) and vitreous amyloidosis (p = 0.025) than non-transplanted patients. Of the 165 eyes with glaucoma, 92.1% had scalloped iris (p < 0.001) and of 32 eyes with retinal amyloidotic angiopathy, 68.8% had vitreous amyloidosis (p < 0.001). All prevalences increased with time of disease. The earliest ocular manifestations were abnormal Schirmer test and abnormal TBUT (12% and 17% at 5 years of clinical disease) and the least prevalent was retinal amyloid angiopathy (8% at 15 years of clinical disease). CONCLUSION: Ocular disorders in FAP patients are common, and their prevalence increases with disease duration. Prevalence is influenced by several factors, such as the age at onset of FAP and liver transplantation.

Impact of liver transplantation on the natural history of oculopathy in Portuguese patients with transthyretin (V30M) amyloidosis.

PURPOSE: Evaluation of the impact of liver transplantation in the natural history of ocular disorders in familial amyloidotic polyneuropathy (FAP) amyloidosis TTR V30M related (ATTR V30M) patients. DESIGN: A clinical, retrospective and cross-sectional study of 64 Portuguese FAP ATTR V30M patients was carried out between January 2005 and December 2011. METHODS: Thirty-two liver transplanted patients (both eyes) aged 39.6-53.8 years old, 32/32 male/female, were paired with an equal number of non-transplanted patients, matching for age, gender, age at onset, disease duration and gender of transmitting parent. Intervention or observation procedure: Routine ophthalmological observation. MAIN OUTCOME MEASURES: Slit-lamp observation for abnormal conjunctival vessels (ACV), tears break-up time, iris, lens; fundus observation for vitreous, retina and optic disc; Schirmer test. RESULTS: Liver transplantation had no influence on tears break-up time, deposition of amyloid on the iris and retinal amyloid angiopathy. Slight, non-statistically significant protective effects of liver transplantation were noted in the first years for some ocular manifestations (ACV and scalloped iris), except for the abnormal Schirmer test, which was significantly more prevalent in non-transplanted patients' eyes (81% versus 56%, p = 0.002). On the other hand, deposition of amyloid on the lens, vitreous amyloidosis and glaucoma were apparently more common in transplanted patients. Those differences tended to disappear with time. CONCLUSIONS: Ocular manifestations of FAP were not influenced by liver transplantation in a meaningful way. Both transplanted and non-transplanted FAP patients need similar regular follow-up due to long-term risk of serious ocular disease.