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.

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.

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.

Purpose: To compare the functional and anatomical outcomes after a 0.2 µg/day fluocinolone acetonide (FAc) implant between vitrectomized and nonvitrectomized eyes with chronic diabetic macular edema (DME). Methods: This is a retrospective, comparative analysis of 43 eyes with chronic DME. All eyes were treated with a single 0.2 µg/day FAc implant and followed up for a mean period of 8.5 months (median, 6.0 months; range, 1-21 months). The patients with a 0.2 µg/day FAc implant were divided into 2 groups: 24 eyes which had undergone pars plana vitrectomy prior to 0.2 µg/day FAc (group 1) and 19 eyes which had not been vitrectomized (group 2). Outcome measures included mean changes in best corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters, central subfield foveal thickness (CSFT), and intraocular pressure (IOP), and were measured prior to administration of the 0.2 µg FAc implant, in the first week, at month 1, and quarterly thereafter. Results: Following the 0.2 μg/day FAc implant, the mean change in BCVA at the last observation point, from baseline, was +16.9 ± 3.39 (mean ± SE) letters (p ≤ 0.001) in group 1 and +8.2 ± 4.62 letters (p = 0.092) in group 2. From baseline, a gain of ≥15 letters was achieved in 37.5 and 36.8% of the eyes in group 1 and group 2, respectively. Additionally, an improvement in vision ≥20/40 in 29.2% of group 1 and 15.8% of group 2 was observed. The mean change in CSFT was -217.7 ± 40.8 µm and -155.6 ± 43.4 µm in group 1 and group 2, respectively. The mean change in IOP was +1.6 ± 0.7 mm Hg in group 1 and +0.8 ± 1.3 mm Hg in group 2, relative to baseline. At the last observation point, there were no significant differences between groups 1 and 2 (p > 0.05) in terms of their changes in BCVA, CSFT, and IOP. Conclusion: The results from the real-life practice study demonstrate that the 0.2 μg/day FAc implant is effective and well tolerated in vitrectomized and nonvitrectomized eyes of patients with chronic DME. Our results support the use of a 0.2 μg/day FAc implant to obtain long-term functional and anatomical improvements (mean, 8.5 months; median, 6.0 months) in vitrectomized and nonvitrectomized eyes.

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.

PurposeThe aim of this study was to evaluate the long-term real-world effectiveness of FAc and DEX implants in vitrectomized DME eyes in a real-world setting.MethodsThis was a non-interventional, retrospective, comparative study of 46 vitrectomized eyes in 33 patients with persistent or recurrent DME quantified best-corrected visual acuity (BCVA), central foveal thickness (CFT) and intraocular pressure (IOP) over up to 37 months.ResultsBoth FAc and DEX treatment led to statistically and clinically significant improvements in BCVA and CFT. FAc >10-letter improvement on the Early Treatment Diabetic Retinopathy Study [ETDRS] chart over months 3–24 and a sustained ~200 µm CFT reduction over months 1–24; DEX: >5-letter improvement on the ETDRS chart at months 1 and 3 and >100 µm CFT reduction at month 1. FAc demonstrated sustained, stable and predictable effects on BCVA and CFT over 24 months and also improved BCVA and decreased CFT in a cohort of DME eyes that was refractory to DEX over 6 months.ConclusionThis real-world study demonstrates long-term effectiveness of FAc in vitrectomized DME eyes and sustained effectiveness in DME eyes that did not respond to DEX therapy.

Purpose: To evaluate pars plana vitrectomy (PPV) outcomes in cases with tractional diabetic macular edema (tDME). Methods: We conducted a single-center retrospective study with a follow-up of 12 months. Forty-six eyes with tDME of 38 patients submitted to PPV between 2013 and 2015 were assessed. A standard PPV was performed and surgical outcomes were registered at the 3-, 6-, and 12-month follow-up. Results: The baseline median best corrected visual acuity (BCVA) in ETDRS (Early Treatment Diabetic Retinopathy Study) letters and the median central foveal thickness (CFT) were 43.0 letters and 491.0 µm, respectively. At the 12-month follow-up, a median decrease in CFT of 232.7 µm was observed. A CFT < 300 µm was achieved in 65.2% of the cases (52.2% needing no further treatment); a BCVA improvement by ≥10 letters was achieved in 60.0%, but there was a decrease of ≥10 letters in 13.0% of the cases. DME recurrence was observed in 10.9% of the cases, with a median time of development after vitrectomy of 6 months. As a major postoperative complication, a macular hole was observed in 1 patient (2.1%). Conclusions: In our series, PPV for tDME induced an improvement in retinal thickening and visual outcome in more than 50% of the cases, with low recurrence rates and a low number of postoperative complications.

Purpose: The primary objective of this study was to better understand the epidemiological risk factors associated with severe eye injury of patients and the secondary objective was to evaluate functional outcomes of these severe eye injuries. Methods: A retrospective, noncomparative cohort study of severe ocular trauma, in patients assessed in an emergency room from January 2004 to December 2018 at Centro Hospitalar Universitário do Porto was performed and statistically analyzed. Results: This study included a total of 751 patients (758 eyes) suffering ocular trauma. Men had a higher rate of ocular trauma than women (81.4% vs 18.6%). The mean age was 48.9 years old. The most common types of injury were rupture (33.8%) and penetrating (20.9%). Work-related accidents were responsible for 19.3% of injuries. Home was the most common location of trauma (46.3%). In 8.8% of trauma the best corrected visual acuity at presentation was superior to 20/40 while in 6.5% of cases no light perception (NLP) was registered. In 44.8% of trauma the best corrected visual acuity at last follow-up visit (BCVAF) was superior to 20/40 while in 15.7% of cases NLP was registered. Conclusion: The epidemiological high-risk factors identified were: adult males, economic crisis, home, blunt objects in man and falls in woman. Future primary prevention should take into account these factors. This study also demonstrated an important visual impairment associated with severe ocular trauma, even with timely surgical treatment, with BCVAF of NLP in 15.7% of cases.