Intensive urate-lowering with pegloticase plus methotrexate co-therapy in uncontrolled gout patients with and without chronic kidney disease: A retrospective case series.

Chronic kidney disease (CKD) and gout commonly co-occur. Pegloticase lowers serum urate (SU) in uncontrolled gout patients but antidrug antibodies limit urate-lowering response and increase infusion reaction (IR) risk. Methotrexate (MTX) co-administration increases pegloticase response rate and mitigates IR risk but CKD limits MTX use. This pooled case series examined pegloticase + MTX co-therapy in uncontrolled gout patients with and without CKD. Cases of pegloticase + MTX co-therapy in existing datasets were retrospectively examined. Baseline eGFR classified patients as CKD (eGFR < 60 mL/min/1.73 m2) or non-CKD (eGFR ≥ 60 mL/min/1.73 m2). Patient characteristics, treatment parameters, laboratory values, urate-lowering response rate (≥12 pegloticase infusions received and SU < 6 mg/dL just before infusion 12), and AEs were examined. Fifteen CKD (eGFR: 43.2 ±â€…11.3 mL/min/1.73 m2; SU: 8.6 ±â€…2.2 mg/dL), 27 non-CKD (eGFR: 82.9 ±â€…19.0 mL/min/1.73 m2; SU: 9.5 ±â€…1.7 mg/dL) patients were included. Comorbidity profiles were similar, but CKD patients were older (72.0 ±â€…9.9 vs 52.3 ±â€…14.3 years) and more often female (33.3% vs 7.4%). Treatment parameters were similar with 4-week MTX Run-in followed by mean of 14.7 ±â€…8.1 [CKD] vs 14.1 ±â€…7.1 [non-CKD] pegloticase infusions. However, CKD patients had lower MTX dose (14.8 ±â€…5.8 vs 19.3 ±â€…4.9 mg/week). Urate-lowering response was similar (92% vs 86%). eGFR increased during treatment in 60% of CKD (+11.5 ±â€…20.9 mL/min/1.73 m2, 87% stable/improved CKD-stage) and 44% of non-CKD (+4.2 ±â€…15.0 mL/min/1.73 m2) patients. AEs were similar (≥1 AE CKD: 53%, non-CKD: 67%; gout flare most-reported). One case each of pancytopenia and IR (mild) occurred in non-CKD patients. These real-world data show similar pegloticase + MTX efficacy in CKD and non-CKD patients. No new safety signals were identified, with most CKD patients showing renal function stability or improvement during therapy.

Challenges for further successful development of tumor necrosis factor targeting therapies for uveitis.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU. AREAS COVERED: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated. EXPERT OPINION: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.

Considerations in the management of ocular toxoplasmosis in pregnancy: a review of literature.

Ocular toxoplasmosis is the most common cause of infectious posterior uveitis. Available literature is still conflicting regarding the incidence of recurrence during pregnancy as various calculations were employed in the different published studies. Although earlier reports have suggested a difference in presentation and an increase in severity during pregnancy, newer studies appear to show otherwise. Further diagnostic testing, including serologic and intraocular fluid sampling, may be indicated to increase the diagnostic accuracy in this special population of patients. The management of ocular toxoplasmosis during pregnancy is challenging as the foetus is additionally considered in the choice of treatment. Traditionally preferred anti-toxoplasmosis regimens containing antifolate drugs, such as pyrimethamine and trimethoprim-sulfamethoxazole, cannot be used routinely in pregnant patients, especially during the first trimester. This review includes literature on alternative treatments for ocular toxoplasmosis during pregnancy, including spiramycin and intravitreal treatment options.

Recent advances in uveitis therapy: focus on selected phase 2 and 3 clinical trials.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract. It is a leading cause of blindness in developed countries and exerts significant psychological, social, and economic impact on both patients and the larger society. While there are numerous pharmacotherapy options, posterior segment noninfectious uveitis remains a significant challenge to treat due to its severity, chronicity, and high recurrence rates. AREAS COVERED: The index review highlights the unmet needs of uveitis pharmacotherapy and its research and the shortcomings of existing ocular and systemic therapeutic options for noninfectious uveitis. The more promising novel ocular drug delivery methods and therapeutic targets/drugs are discussed, and evidence from the clinical trials is evaluated. EXPERT OPINION: There has been incredible growth in the number of treatment options available to uveitis patients today, especially with the new generation of biologic drugs. Available evidence suggests that these newer options may be superior to conventional immunosuppressive therapies in terms of efficacy and side effect profiles. Further high-quality research and additional clinical trials will be needed to clarify their roles in the stepladder treatment approach of noninfectious uveitis.

Ocular tuberculosis masquerading as atypical ocular toxoplasmosis.

Ocular tuberculosis is a great mimicker of various uveitis entities. We present a case of a 29-year-old male who came in with blurring of vision and floaters in the left eye. On examination, the left eye had anterior chamber cells and vitritis associated with retinitis. He had no other symptoms. The initial presentation was consistent with ocular toxoplasmosis, and he was started on oral sulfamethoxazole-trimethoprim and showed a good response to the treatment. However, work-up revealed negative toxoplasma antibody titers but a positive M. tuberculosis interferon-gamma release assay test and Mantoux test, making the diagnosis of ocular tuberculosis more likely. The patient was shifted to antituberculous therapy, which eventually resulted in the resolution of the inflammation with a recovery of the visual acuity. The diagnosis of ocular tuberculosis requires a detailed medical history as well as microbiologic and immunologic studies. A high index of suspicion by the treating ophthalmologist is necessary to reveal the diagnosis.

Neurosarcoidosis, Coccidioidomycosis, or Both!

Purpose: To report a case of neurosarcoidosis (NS) who was initially diagnosed as Coccidioidomycosis immitis (CI) infection. Observations: A 57-year-old diabetic man presented with sudden painless diminution of vision, metamorphopsia, and color vision deficits in the left eye (OS) for one month. His vision was 20/20 in the right eye (OD) and 20/40 OS. Ophthalmic examination revealed left relative afferent pupillary defect, blurred optic nerve margin, creamy chorioretinal infiltration around the optic disc, and mild macular edema. OD examination was non-revealing. Chest CT scan with contrast showed calcified mediastinal lymph nodes, but biopsy of the lymph nodes was normal. Brain and orbit MRI demonstrated soft tissue abnormality with enhancement in left orbital apex with involvement of the extraocular muscles. CSF culture was negative, but complement fixation had positive titer of 1:2 for CI. The patient was diagnosed with CI meningitis, and antifungal therapy was initiated. Slight visual and symptomatic improvement was observed, which was not completely satisfactory. Biopsy of extraocular orbital muscle five months later revealed non-caseating granulomatous inflammation, leading to initiation of prednisone trial therapy. Nine months later, the patient was referred to a tertiary center owing to persistence of optic disc edema OS. PET CT was consistent with a diagnosis of sarcoidosis. Antifungal treatment was discontinued, and oral prednisone with methotrexate was initiated. Subsequently, methotrexate was replaced by infliximab to further manage ocular inflammation and neurologic symptoms which was effective. Vision was 20/20 OD and 20/30 OS at the most recent visit. Conclusion and Importance: Signs and symptoms of neurosarcoidosis and coccidioidomycosis can be similar and deceiving. The index case underscores importance of considering appropriate differential diagnoses in patients with similar symptoms and signs who may respond to preliminary designated treatment but not to the optimal extent. Considering such possibility could assist clinicians in managing the patients timely and efficiently.

Community Practice Experiences with a Variety of Immunomodulatory Agents Co-Administered with Pegloticase for the Treatment of Uncontrolled Gout.

OBJECTIVE: Patients with uncontrolled/refractory gout have heavy disease burden, but few treatment options. Pegloticase lowers serum urate (SU), but anti-drug antibodies can limit treatment efficacy. Evidence supports immunomodulator-pegloticase co-administration to increase sustained urate-lowering rates, but published cases are limited. This study investigated experience with pegloticase-immunomodulation co-therapy at two community rheumatology practices. METHODS: Patients initiating pegloticase with immunomodulation in 2017 or later were included. Patient/treatment characteristics and proportion of responders (≥ 12 pegloticase infusions, SU < 6 mg/dl at infusion-12) were examined. Patients on therapy at data collection with < 12 infusions were excluded from response analyses. eGFR before and after therapy was examined. RESULTS: Thirty-four patients (79% male, 62.4 ± 16.3 years) with uncontrolled gout (SU = 9.1 ± 2.0 mg/dl, 91% tophaceous) were included. Most-reported comorbidities were hypertension (76%), obesity (71%), osteoarthritis (68%), and CKD (47%). Pre-therapy eGFR was 65.4 ± 25.2 ml/min/1.73 m2 (41% eGFR < 60 ml/min/1.73 m2). All patients initiated immunomodulation before (5.3 ± 3.0 weeks, n = 32) or at (n = 2) first pegloticase infusion. Subcutaneous methotrexate (15.4 ± 4.9 mg/week, n = 20), oral methotrexate (15.3 ± 3.6 mg/week, n = 9), mycophenolate mofetil (1000 mg/day, n = 3), and azathioprine (100 mg/day, n = 2) were administered. Patients received 14.6 ± 7.1 infusions over 28.5 ± 14.9 weeks. Overall response rate was 89%, ranging among immunomodulators (subcutaneous methotrexate: 93%, oral methotrexate: 89%, mycophenolate mofetil: 100%, azathioprine: 50%). On average, eGFR increased during therapy (+ 10.3 ± 16.9 ml/min/1.73 m2), with CKD stability/improvement in 85%. Nineteen patients (56%) experienced gout flares. No infusion reactions or infections were noted. No new safety concerns were identified. CONCLUSIONS: These real-world findings provide further support for increased pegloticase response rates when co-treatment with immunomodulating therapy is used.

Patients with gout that does not respond to oral urate-lowering therapies have heavy disease burden and few treatment options. Pegloticase lowers serum urate levels (SU) and resolves tophi, but anti-drug antibodies can limit urate-lowering efficacy duration. Evidence increasingly supports co-administering an immunomodulator with pegloticase to increase the proportion of patients with sustained urate-lowering response. However, there are few published cases from real-world clinical practice. This study examined treatment with pegloticase + immunomodulation at two community rheumatology practices. Patients who began treatment with pegloticase and an immunomodulator in 2017 or later were included. The proportion of patients with sustained urate-lowering response (≥ 12 infusions received, SU < 6 mg/dl at infusion 12) was investigated. Renal function before and after therapy was also examined. Thirty-four patients were included. Before treatment, SU averaged 9.1 mg/dl and most-reported comorbidities were hypertension (76%), obesity (71%), osteoarthritis (68%), and chronic kidney disease (47%). All patients began using an immunomodulator before or at first pegloticase infusion (subcutaneous methotrexate [20 patients], oral methotrexate [9 patients], mycophenolate mofetil [3 patients], and azathioprine [2 patients]). On average, 14.6 infusions were administered over 28.5 weeks and overall response rate was 89%. Response rate varied among different immunomodulators: subcutaneous methotrexate: 93%, oral methotrexate: 89%, mycophenolate mofetil: 100%, azathioprine: 50%. On average, kidney function improved, with chronic kidney disease stage stability/improvement in 85% of patients. Nineteen patients (56%) experienced gout flares. No infusion reactions or infections were noted and no new safety concerns were identified. These real-world findings provide further support for administering immunomodulation as co-therapy to pegloticase.

Combined central retinal artery and vein occlusion following trabeculectomy.

Retinal vascular events may occur as rare complications of glaucoma procedures due to various factors, including exacerbation of ischemia in patients with pre-existing vascular comorbidities, toxic effect of mitomycin-C, and decompression retinopathy. We present the case of a 47-year-old hypertensive male who underwent trabeculectomy for advanced glaucoma in his right eye. At 3 weeks postoperatively, he presented with a drop in visual acuity to light perception with a spike in intraocular pressure. On examination, there was increased bleb vascularity as well as rubeosis. Fundoscopy revealed findings consistent with both central retinal artery occlusion and central retinal vein occlusion. Combined central retinal artery and vein occlusion is a rare retinal vascular condition. Neovascular glaucoma can occur as a sequelae of the ischemic process in the retina. Despite treatment, there is a poor visual prognosis, with the affected eye usually becoming blind from optic atrophy and neovascularization.

Optical coherence tomography angiography analysis of changes in the foveal avascular zone in eyes with diabetic macular edema treated with intravitreal anti-vascular endothelial growth factor.

BACKGROUND: To analyze the changes in foveal avascular zone (FAZ) area, perimeter, and circularity in the superficial (SCP) and deep (DCP) capillary plexuses in eyes with diabetic macular edema (DME) treated with intravitreal anti-VEGF using optical coherence tomography angiography (OCTA). METHODS: This prospective observational study included 56 eyes from 32 patients with DME that received intravitreal anti-VEGF. OCTA images were obtained at baseline and 1, 3, and 6 months of follow-up. The outcome measures were FAZ area, perimeter, and circularity in both the SCP and DCP, as well as central subfield thickness (CST) and best-corrected visual acuity (BCVA). RESULTS: The mean number of intravitreal anti-VEGF injections received during the observation period was 4.60 ± 0.82 (range: 3-6). The FAZ area, perimeter, and circularity were statistically unchanged at all observation points in both the SCP (p = 0.772, p = 0.405, p = 0.157, respectively) and the DCP (p = 0.620, p = 0.769, p = 0.481, respectively). Despite having no change in the FAZ parameters, there was still a statistically significant decrease in CST (p < 0.001) as well as a statistically significant increase in BCVA (p = 0.004) during the observation period. CONCLUSIONS: The FAZ area, perimeter, and circularity in the SCP and DCP as measured by OCTA remained stable during the first 6 months of intravitreal anti-VEGF therapy in eyes with DME. While there were no significant changes in the FAZ, treatment with intravitreal anti-VEGF still resulted in decreased CST and improved BCVA.

Expert Opinion on Pegloticase with Concomitant Immunomodulatory Therapy in the Treatment of Uncontrolled Gout to Improve Efficacy, Safety, and Durability of Response.

PURPOSE OF REVIEW: Gout is a systemic disease from which some patients develop numerous painful tophi that adversely affect quality of life and functionality. Some patients treated with oral urate-lowering therapy are unable to maintain serum urate levels below 6 mg/dL, and these patients, thus classified as having refractory or uncontrolled gout, often require therapy with pegloticase to reduce symptoms and tophaceous burden. The objective of this expert opinion review is to summarize the available evidence supporting the use of concomitant immunomodulators with pegloticase to prevent development of anti-drug antibodies (ADAs) when treating patients with uncontrolled gout. RECENT FINDINGS: Emerging evidence suggests that adding an immunomodulator to pegloticase therapy can substantially increase response rates to double those observed in phase 3 randomized controlled trials. The combination of immunomodulation with pegloticase should be considered in routine clinical practice to improve durability of response, efficacy, and safety among patients with uncontrolled gout who otherwise have limited therapeutic options.

Zinc protoporphyrin binding to telomerase complexes and inhibition of telomerase activity.

Zinc protoporphyrin (ZnPP), a naturally occurring metalloprotoporphyrin (MPP), is currently under development as a chemotherapeutic agent although its mechanism is unclear. When tested against other MPPs, ZnPP was the most effective DNA synthesis and cellular proliferation inhibitor while promoting apoptosis in telomerase positive but not telomerase negative cells. Concurrently, ZnPP down-regulated telomerase expression and was the best overall inhibitor of telomerase activity in intact cells and cellular extracts with IC50 and EC50  values of ca 2.5 and 6 µM, respectively. The natural fluorescence properties of ZnPP enabled direct imaging in cellular fractions using non-denaturing agarose gel electrophoresis, western blots, and confocal fluorescence microscopy. ZnPP localized to large cellular complexes (>600 kD) that contained telomerase and dysskerin as confirmed with immunocomplex mobility shift, immunoprecipitation, and immunoblot analyses. Confocal fluorescence studies showed that ZnPP co-localized with telomerase reverse transcriptase (TERT) and telomeres in the nucleus of synchronized S-phase cells. ZnPP also co-localized with TERT in the perinuclear regions of log phase cells but did not co-localize with telomeres on the ends of metaphase chromosomes, a site known to be devoid of telomerase complexes. Overall, these results suggest that ZnPP does not bind to telomeric sequences per se, but alternatively, interacts with other structural components of the telomerase complex to inhibit telomerase activity. In conclusion, ZnPP actively interferes with telomerase activity in neoplastic cells, thus promoting pro-apoptotic and anti-proliferative properties. These data support further development of natural or synthetic protoporphyrins for use as chemotherapeutic agents to augment current treatment protocols for neoplastic disease.

Changes in Retina Practice Patterns During the COVID-19 Pandemic in the Philippines.

PURPOSE: The aim of this study was to assess the changes in clinical practice patterns among retina specialists in the Philippines in response to the coronavirus disease 2019 (COVID-19) pandemic. MATERIALS AND METHODS: This was a multi-center cross-sectional study based on a self-reported online survey. An online questionnaire was distributed among practicing retina specialists in the Philippines as listed in the database of the Vitreo-Retina Society of the Philippines using a combination of convenience and snowball sampling. The questionnaire contained questions regarding changes in clinic set-up, laser procedures, intravitreal injections, vitreoretinal surgery, and long-term outlooks. RESULTS: A total of 48 responses were recorded and analyzed with a view rate of 41.7%. There was a decrease in the number of clinic consults, laser procedures, intravitreal injections, and vitreoretinal procedures with most reporting only 1-25% of their usual patient load. Several modifications in clinic protocols have been made, including use of personal protective equipment, adjustments in clinic hours, and scheduling of only urgent cases. The adjustments implemented during the pandemic are expected by most respondents to be long-term changes. CONCLUSION: Retina specialists in the Philippines have implemented changes in their practices to combat COVID-19, following guidelines issued by the local and international governing bodies on health.

Retinal vasoproliferative tumour secondary to retinitis pigmentosa sine pigmento.

Retinitis pigmentosa can be associated with exudative vasculopathy in rare instances, which can manifest as retinal vasoproliferative tumours. We present the case of a 33-year-old woman previously diagnosed with retinitis pigmentosa sine pigmentosa in both eyes. She was asymptomatic and just came in for a routine follow-up eye examination. Thorough examination of the peripheral retina on the right eye revealed a dome-shaped retinal tumour with a feeder vessel and surrounding exudative changes at the superotemporal periphery, consistent with a secondary retinal vasoproliferative tumour from retinitis pigmentosa. She subsequently underwent focal laser photocoagulation of the tumour which resulted in tumour stabilisation. While exudative vasculopathy is very uncommon in retinitis pigmentosa, ophthalmologists need to be aware of its occurrence in such patients. Vision loss may occur from exudation, haemorrhage, retinal detachment and neovascularisation. A thorough examination of the peripheral retina is warranted in these cases.

Tractional retinal detachment ('crunch' phenomenon) from intravitreal anti-vascular endothelial growth factor injection in central retinal vein occlusion.

Tractional retinal detachment is an uncommon complication of intravitreal anti-vascular endothelial growth factor (VEGF) injection wherein the drug triggers tractional retinal detachment as a result of fibrovascular membrane contraction. We present a case of a 42-year-old hypertensive woman diagnosed with chronic central retinal vein occlusion on both eyes. The right eye had total retinal detachment and neovascular glaucoma, while the left eye had retinal neovascularisation. Panretinal photocoagulation and intravitreal anti-VEGF injection was started on the left eye. However, she was lost to follow-up. She returned 4 months later with extensive tractional retinal detachment involving the macula on the left eye. She subsequently underwent vitrectomy with endolaser and silicone oil tamponade on the left eye. The anti-VEGF 'crunch' results from regression of fibrovascular proliferation with a concurrent increase in fibrosis, resulting in worsening retinal traction. With the widespread use of anti-VEGF agents, ophthalmologists need to be aware of this vision-threatening complication.

The effect of immunomodulators on the efficacy and tolerability of pegloticase: a systematic review.

INTRODUCTION: Pegloticase is a recombinant PEGylated uricase that converts relatively insoluble urate to highly water-soluble allantoin, which is readily excreted by the kidneys. It is the first and only biologic treatment indicated for refractory or uncontrolled gout. Clinical trials showed a 6-month pegloticase responder rate of 42%, with the non-responder rate largely being attributed to the development of high-titer anti-drug antibodies (ADAs) against pegloticase. Immunomodulation attenuates ADA formation to biologics in a number of autoimmune conditions, but their use with pegloticase for uncontrolled gout is less established. This systematic review examined published cases of refractory gout patients treated with immunomodulation in combination with pegloticase. METHODS: Published cases of immunomodulation with pegloticase were identified in a PubMed search and in abstract databases of major rheumatology society meetings (2012-2020). Duplicate and review articles were excluded, as were those that did not include cases of pegloticase use with immunomodulation. Cases with off-label pegloticase administration schedules were also excluded. Pegloticase response was defined according to each study's specified standard. RESULTS: Ten publications describing 82 cases of pegloticase use in the setting of immunomodulation were identified. Overall pegloticase response rate was 82.9%. Patients co-treated with an individual immunomodulator had the following response rates: methotrexate: 87.5% (35 of 40 patients), mycophenolate mofetil: 86.4% (19 of 22 patients vs. pegloticase monotherapy [placebo]: 40% [4 of 10 patients]), azathioprine: 63.6% (7 of 11 patients), and leflunomide: 66.7% (4 of 6 patients). A single patient was co-treated with cyclosporin and was a responder. The two patients treated with more than one immunomodulator were both responders. CONCLUSION: Published reports suggest that immunomodulation co-therapy has the potential to markedly improve pegloticase responder rates in patients with uncontrolled gout.

Large graft tectonic penetrating keratoplasty in a case of severe aspergillus keratitis.

Penetrating keratoplasty is indicated for cases of severe microbial keratitis, particularly if associated with impending corneal perforation. The case report details a 45-year-old male farmer who consulted for blurring of vision in the left eye after an incident wherein mud was flung onto his eye during farming. He noted eye redness and a growing opacity on his left eye. He was initially treated with topical antimicrobial and corticosteroid medication which did not resolve his symptoms. He presented with a visual acuity of hand movement on the affected eye. Slit lamp examination showed a large protruding mound-like plaque, occupying almost the entire corneal surface of the left eye, with associated scleritis. The ocular ultrasound was unremarkable. The patient was diagnosed with fungal keratitis, which culture from corneal scraping showed to be from an infection with Aspergillus. A tectonic penetrating keratoplasty with 360-degree iridectomy, lens extraction, and anterior vitrectomy was immediately done, and a regimen consisting of topical natamycin was started. Despite the severe presentation of the fungal corneal infection, the eye was fortunately salvaged.

Increased Efficacy and Tolerability of Pegloticase in Patients With Uncontrolled Gout Co-Treated With Methotrexate: A Retrospective Study.

INTRODUCTION: Gout is a painful inflammatory condition caused by chronically elevated serum uric acid levels (sUA). When standard urate-lowering therapies fail/are not tolerated, uncontrolled gout (elevated sUA, subcutaneous tophi, chronic gouty arthritis, frequent flares) can occur. Pegloticase, a recombinant uricase, converts uric acid to allantoin, a readily excreted molecule. Responder rate in trials was 42%, limited by anti-drug antibody (ADA) development. Immunomodulators attenuate ADA formation and case reports suggest immunomodulation increases pegloticase responder rates. The current study retrospectively examined responder rate in patients undergoing methotrexate/pegloticase co-therapy. METHODS: Patients who underwent methotrexate/pegloticase co-treatment at a single rheumatology practice were included. Demographics, clinical, treatment, and safety parameters were collected. The primary outcome was the proportion of responders (≥ 12 biweekly pegloticase infusions, sUA < 6 mg/dl just prior to infusion 12). RESULTS: Ten patients (nine men, 52.3 ± 13.5 years) with uncontrolled tophaceous gout (erosive damage, ulcerative tophi, frequent flares, gout-related hospitalizations) were included. Patients had failed allopurinol (100-300 mg) or febuxostat (40 mg) therapy (doses not increased because of intolerance, kidney concerns, noncompliance, or rapid tophi resolution requirement). Baseline sUA was 9.42 ± 2.05 mg/dl. Along with standard pre-infusion prophylaxis, nine patients received subcutaneous methotrexate (25 mg/week) initiated 14-35 days before pegloticase and one patient received oral methotrexate (12.5 mg/week) initiated 14 days after pegloticase. Eight patients (80%) were responders, receiving 15.5 ± 3.8 infusions (range, 12-21) over 31.8 ± 9.5 weeks. One patient had efficacy loss with mild infusion reaction during infusion 4 and one patient was lost to follow-up after infusion 5. One patient reported one gout flare. No new safety concerns emerged. CONCLUSIONS: Methotrexate/pegloticase co-therapy resulted in a higher responder rate than the established 42% with pegloticase alone. Therefore, methotrexate/pegloticase co-therapy may safely allow more patients to benefit from a full treatment course, likely through ADA attenuation.

Uncontrolled gout is a painful inflammatory condition caused by excess uric acid in the blood. When standard oral medicines used to lower uric acid do not work or cannot be taken, pegloticase is the only remaining treatment option. Unfortunately, less than half of patients respond to pegloticase for an adequate amount of time because their immune system develops antibodies against the medicine, causing the medicine to be quickly removed from the body preventing a durable or prolonged response. Methotrexate has been shown to limit or prevent this immune response in patients treated with biologic therapies for autoimmune diseases. The current study found that eight of ten patients (80%) treated with both methotrexate and pegloticase responded to treatment (received 12 or more biweekly pegloticase doses and had low uric acid levels in their blood just before infusion 12). No new side effects or safety concerns were reported. In this retrospective study, methotrexate appeared to allow more patients to benefit from a full course of pegloticase therapy.

Corneal melt following corneal tattooing with carbon-based ink.

PURPOSE: to report a case of corneal melting following corneal tattooing with carbon-based ink. OBSERVATIONS: A 67 year old female with a phthisical eye underwent corneal tattooing with carbon-based ink for purpose of cosmesis. The procedure was uncomplicated. At 8 weeks postoperatively, she presented with almost complete corneal melt with uveal prolapse. There was no evidence of infection. The patient underwent evisceration. Histopathologic examination of the excised corneal button showed melting of the epithelium and anterior stromal layers, diffuse inflammation of the deeper stromal layers, and disorganized Descemet membrane and endothelium with adherent iris tissue. CONCLUSIONS AND IMPORTANCE: Corneal melting can occur as a rare complication of corneal tattooing with carbon-based ink.

Transscleral cyclophotocoagulation as primary management in a nanophthalmic eye with anterior uveitis and secondary mixed mechanism glaucoma.

A 36-year-old woman presented with eye pain and blurring of vision in her right eye. On eye examination, it was noted that there were angle-closure glaucoma and anterior uveitis in both eyes. Ocular ultrasound showed short axial lengths as well as a choroidal thickening in both eyes, confirming the diagnosis of nanophthalmos. Nanophthalmos is a condition where the eye is abnormally short, resulting in axial hyperopia and predisposing it to angle-closure glaucoma. The patient was initially managed medically, but the glaucoma was intractable. The patient underwent repeated sessions of transscleral cyclophotocoagulation which eventually lowered the intraocular pressure. The management of nanophthalmic eyes can be quite challenging due to the risk of inciting uveal effusion syndrome with any form of intraocular surgery. Controlled and repeated sessions of transscleral cyclophotocoagulation may be considered as a viable management option in these cases.