Purpose
To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the administration of antirheumatic ...drugs.
Methods
A systematic literature search was performed using the PubMed, MEDLINE, and EMBASE databases. In addition, a cohort of 489 RA patients who attended the Authors’ departments were examined.
Results
Keratoconjunctivitis sicca, episcleritis, scleritis, peripheral ulcerative keratitis (PUK), and anterior uveitis were diagnosed in 29%, 6%, 5%, 2%, and 10%, respectively, of the mentioned cohort. Ocular ADRs to non-steroidal anti-inflammatory drugs are rarely reported and include subconjunctival hemorrhages and hemorrhagic retinopathy. In patients taking indomethacin, whorl-like corneal deposits and pigmentary retinopathy have been observed. Glucocorticoids are frequently responsible for posterior subcapsular cataracts and open-angle glaucoma. Methotrexate, the prototype of disease-modifying antirheumatic drugs (DMARDs), has been associated with the onset of ischemic optic neuropathy, retinal cotton-wool spots, and orbital non-Hodgkin’s lymphoma. Mild cystoid macular edema and punctate keratitis in patients treated with leflunomide have been occasionally reported. The most frequently occurring ADR of hydroxychloroquine is vortex keratopathy, which may progress to “bull’s eye” maculopathy. Patients taking tofacitinib, a synthetic DMARD, more frequently suffer herpes zoster virus (HZV) reactivation, including ophthalmic HZ. Tumor necrosis factor inhibitors have been associated with the paradoxical onset or recurrence of uveitis or sarcoidosis, as well as optic neuritis, demyelinating optic neuropathy, chiasmopathy, and oculomotor palsy. Recurrent episodes of PUK, multiple cotton-wool spots, and retinal hemorrhages have occasionally been reported in patients given tocilizumab, that may also be associated with HZV reactivation, possibly involving the eye. Finally, rituximab, an anti-CD20 monoclonal antibody, has rarely been associated with necrotizing scleritis, macular edema, and visual impairment.
Conclusion
The level of evidence for most of the drug reactions described herein is restricted to the “likely” or “possible” rather than to the “certain” category. However, the lack of biomarkers indicative of the potential risk of ocular ADRs hinders their prevention and emphasizes the need for an accurate risk vs. benefit assessment of these therapies for each patient.
To compare the efficacy of adalimumab (ADA) and infliximab (IFX) in patients with non-infectious intermediate uveitis, posterior uveitis, and panuveitis. Demographic, clinical, instrumental, and ...therapeutic data from patients enrolled were collected at the start of treatment, at 12-month follow-up, and at the last follow-up assessment. One hundred seven patients (46 females, 187 eyes) were enrolled, 66 (61.7%) treated with ADA and 41 (38.3%) with IFX. Bilateral involvement was observed in 80 cases. The mean follow-up was 26.45 ± 21.71 months for ADA patients and 56.60 ± 56.04 months for IFX patients. The overall decrease of uveitis frequency during the first 12 months of treatment was 66.7% in the IFX group and 84.2% in the ADA group, compared to the previous 12 months (
p
= 0.09). A significantly higher corticosteroid dosage was found among patients treated with ADA at the last follow-up visit (
p
= 0.008). The percentage of patients co-administered with corticosteroids was significantly higher among ADA patients both at the 12-month visit (
p
= 0.03) and at the last visit (
p
= 0.0004). The frequency of uveitic macular edema (UME) was significantly higher among patients treated with ADA compared to those treated with IFX at the 12-month assessment (
p
= 0.015) and at the last follow-up visit (
p
= 0.011); central macular thickness was significantly higher in ADA group compared to the IFX group at the last follow-up assessment (
p
= 0.04). ADA and IFX have shown a similar efficacy in controlling uveitis relapses, but IFX showed a more pronounced corticosteroid sparing effect and a significantly higher capacity in resolving UME compared to ADA.
Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. It is characterized by as yet undisclosed genetic and environmental ...factors affecting the incomplete penetrance.
We identified 27 LHON subjects who possess heteroplasmic primary LHON mutations. Mitochondrial DNA (mtDNA) copy number was evaluated.
The presence of centrocecal scotoma, an edematous, hyperemic optic nerve head, and vascular tortuosity, as well as telangiectasia was recognized in affected subjects. We found higher cellular mtDNA content in peripheral blood cells of unaffected heteroplasmic mutation carriers with respect to the affected.
The increase of cellular mtDNA content prevents complete loss of vision despite the presence of a heteroplasmic state of LHON primary mutation, suggesting that it is a key factor responsible for penetrance of LHON.
The study aim was to evaluate the efficacy of adalimumab (ADA) in a large series of Behçet’s disease (BD)-related uveitis. We performed a multicenter retrospective observational study including 40 ...selected patients (66 eyes) receiving ADA. Clinical data were retrospectively analyzed at baseline, at 3 and 12 months of treatment. Primary end point was reduction of ocular inflammatory flares. Secondary end points were improvement of best corrected visual acuity (BCVA), reduction of macular thickness measured by optical coherence tomography (OCT), reduction in the occurrence of vasculitis assessed by fluorescein angiography (FA), and evaluation of statistically significant differences between patients treated with ADA monotherapy and those undergoing ADA plus DMARDs and in patients firstly treated with ADA compared to patients previously administered with other biologics; ADA steroid sparing effect was also evaluated. During the first 12 months of ADA therapy, the number of flares significantly decreased from 200 flares/100 patients/year to 8.5 flares/100 patients/year (
p
< 0.0001). Similarly, BCVA improved if compared to baseline (7.4 ± 2.9 versus 8.5 ± 2.1,
p
= 0.03). OCT findings significantly improved showing a mean reduction of central macular thickness (CMT) of 27.27 ± 42.8 μm at the end of follow-up (
p
< 0.006). FA identified retinal vasculitis in 22 cases at baseline (55%), 8 (20%) cases after 3 months, and in only one (2.5%) case at 12-month follow-up. FA improvement was highly significant at 3- and 12-month follow-up if compared to baseline (
p
< 0.0001 and
p =
0.006, respectively). ADA is highly effective and safe for the treatment of BD-related uveitis, providing a long-term control of ocular inflammation.
The primary aim of the study was to evaluate the efficacy of tumor necrosis factor (TNF)-α blockers adalimumab (ADA) and infliximab (IFX) in refractory sight-threatening retinal vasculitis (RV) ...during a 12-month follow-up period. Secondary aims were to evaluate (i) any impact of concomitant conventional disease-modifying anti-rheumatic drugs (cDMARDs) and different lines of biologic therapy; (ii) any difference in terms of efficacy between ADA and IFX; (iii) consequences of biotherapies on the best-corrected visual acuity (BCVA); (iv) corticosteroid-sparing effect; and (vi) ocular complications during anti-TNF-α treatment. Demographic, clinical, and therapeutic data were retrospectively collected from the medical records and statistically analyzed. Forty-eight patients (82 eyes) were recruited, 22 (45.8%) of which received IFX and 26 (54.2%) ADA. The percentages of patients achieving RV remission within 3 and 12 months were 54 and 86%, respectively. A significant decrease in RV detection was identified from baseline to 3-month (
p
< 0.0001) and 12-month (
p
< 0.0001) assessments and between 3-month and 12-month visits (
p
= 0.004). No differences were identified in terms of RV resolution between (i) patients undergoing monotherapy and those co-administered with cDMARDs at 3-month (
p
= 0.560) and 12-month (
p
= 0.611) follow-up; (ii) biologic-naïve patients and those already exposed to other biologics at 3-month (
p
= 0.497) and 12-month (
p
> 0.99) visits; and (iii) patients treated with ADA and those treated with IFX (
p
= 0.357). During the study period, a statistically significant corticosteroid-sparing effect was observed (
p
= 0.0002), while BCVA values did not significantly change (
p
= 0.950). Anti-TNF-α monoclonal antibodies have proved excellent results in patients with recalcitrant sight-threatening RV.
Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease characterized by a variable and reduced penetrance. Individuals carrying a primary LHON-causing mitochondrial DNA (mtDNA) ...mutation may either remain asymptomatic lifelong, as unaffected carriers, or develop sudden central visual loss that rapidly aggravates over some weeks. Over the years several genetic/environmental triggers able to modulate the risk of developing LHON have been proposed. We provided data supporting a possible correlation between LHON penetrance and the mtDNA copy number, a raw index of mitochondrial mass, whose increase could represent a compensatory response that cells implement to alleviate the pathogenic effect of the primary LHON-causing mtDNA mutations.
We collected Italian and Spanish subjects harboring one of the three common LHON primary mutations, either in heteroplasmic or homoplasmic status. For each population we were able to discriminate between affected subjects presenting typical clinical tracts of LHON and LHON-causing mutation carriers showing no symptoms correlated with vision loss. Each subject has been characterized for the presence of a LHON primary mutation, for its status of homoplasmy or heteroplasmy, and for the mtDNA content per cell, expressed as relative mtDNA/nDNA ratio respect to controls. Additional clinical information is present for all the Italian subjects.
The aim of the present study was to compare long-term adalimumab (ADA) and infliximab (IFX) retention rates in patients with intermediate, posterior, or panuveitis. Additional aims are as follows: ...(i) to identify any difference in the causes of treatment discontinuation between patients treated with ADA and IFX; (ii) to assess any impact of demographic features, concomitant treatments, and different lines of biologic therapy on ADA and IFX retention rates; and (iii) to identify any correlation between ADA and IFX treatment duration and the age at uveitis onset, the age at onset of the associated systemic diseases, and the age at the start of treatment. Clinical, therapeutic, and demographic data from patients with non-infectious intermediate, posterior, or panuveitis treated with ADA or IFX were retrospectively collected. Kaplan-Meier plot and log-rank (Mantel-Cox) test were used to assess survival curves. One hundred eight patients (188 eyes) were enrolled; in 87 (80.6%) patients, uveitis was associated with a systemic disease. ADA and IFX were administered in 62 and 46 patients, respectively. No statistically significant differences were identified between ADA and IFX retention rates (
p
value = 0.22). Similarly, no differences were identified between ADA and IFX retention rates in relation to gender (
p
value = 0.61 for males,
p
value = 0.09 for females), monotherapy (
p
value = 0.08), combination therapy with conventional disease-modifying antirheumatic drugs (log-rank
p
value = 0.63), and different lines of biologic therapy (
p
value = 0.79 for biologic-naïve patients;
p
value = 0.81 for subjects previously treated with other biologics). In conclusion, ADA and IFX have similar long-term retention rates in patients with non-infectious intermediate, posterior, and panuveitis. Demographic, clinical, and therapeutic features do not affect their long-term effectiveness.
Purpose To compare radial peripapillary capillary (RPC) vascular plexus parameters and peripapillary retinal nerve fiber layer (pRNFL) thickness between Early-Treated Adults with Phenylketonuria ...(ETPKU) and controls. Methods This observational study was a monocentric, case control study including 36 eyes of 36 participants. Among these, 18 were early-treated PKU (ETPKU) and 18 were controls. A SD-OCTA (XR Avanti AngioVue OCTA; Optovue Inc., Fremont, CA) was employed to assess the OCT and OCTA parameters of all the participants. The main outcome measures were the RPC vessels density (VD) %, and the pRNFL thickness. Results The average pRNFL thickness was significantly reduced in ETPKU (110.78 ± 12.48 μm) compared to controls (113.22 ± 13.95 μm), p = 0.046. The mean VD% of the small vessels of the RPC plexus was 52.31 ± 2.2 in ETPKU and 50.71 ± 3.2 in controls ( p = 0.049), while the VD% of all the radial peripapillary capillary plexus (RPCP) was 58.5 ± 2.2 in ETPKU and 55.08 ± 3.4 in controls ( p < 0.001). By contrast, there were no differences in age, sex, and IOP between the two groups. Conclusion Through structural OCT and OCTA, we observed thinning of the nerve fibers accompanied by an increase in perfusion of the RPC plexus. Thus, our conclusions suggest that OCTA may serve as a noninvasive method to identify novel retinal biomarkers in ETPKU.
Purpose
To propose a modified ophthalmic triage system based on simple ophthalmic symptoms, signs and anamnestic data and validate its safety and effectiveness.
Methods
Phase 1 of the study was a ...retrospective review of chart records of patients admitted at the ophthalmic emergencies room (OER); phase 2 was a prospective study conducted on all consecutive patients presenting in the OER between April 1st, 2018, and May 30th, 2018. We selected the following six factors as predictors of urgency levels: altered vision, ocular behavior, color, distress, eye trauma, floaters and flashes. ATSO final score can be eventually converted into risk groups: low-risk group (scoring 0–3), intermediate-risk group (scoring 4–5) and high-risk group (scoring > 6).
Results
A total of 953 consecutive patients who presented to our OER over a two-month period were considered for participation in the study. The male-to-female ratio was 1.24:1. The mean age of the participants was 53 years (range 18–92, SD 19 years). ATSO score significantly correlated with urgency levels (
p
< .00001). The sensitivity of ATSO in differentiating urgent from non-urgent conditions was 91.4%, and the specificity was 98.2%. All hospitalized patients (30, 3.15%) have been coded as intermediate/high risk according to the ATSO score.
Conclusion
The use of the ATSO score for patients at the OER provides the clinician with a reliable predictor of urgency, being at the same time safe and effective. The ATSO score may represent a valuable tool to implement triage of ocular patients in the emergency department.
Objective. To assess the efficacy of biologic drugs, beyond tumor necrosis factor- (TNF-) α inhibitors, in the management of noninfectious refractory scleritis, either idiopathic or associated with ...systemic immune-mediated disorders. Patients and Methods. This is a retrospective study assessing the efficacy of several biologic agents (rituximab, anakinra, tocilizumab, and abatacept) and the small molecule tofacitinib in the treatment of scleritis through assessment of scleral inflammation and relapses, as well as treatment impact on best-corrected visual acuity (BCVA) and safety profile. Results. Fourteen patients (19 eyes) were enrolled in the study. Scleritis inflammatory grading significantly improved from baseline to 3 months (p=0.002) and from baseline to the last follow-up visit (p=0.002). Scleritis relapses significantly decreased between the 12 months preceding and following biologic therapy (p=0.007). No differences regarding BCVA were observed (p=0.67). Regarding adverse events, only one patient developed pneumonia and septic shock under rituximab treatment. Conclusions. Our results, though limited to a low number of patients, highlight the effectiveness of different biologic therapies in the treatment of noninfectious refractory scleritis, showing to control scleral inflammation and allowing a significant reduction in the number of relapses.
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