A 56-year-old man introduced for 3 weeks of intermittent blurred imaginative and prescient and photophobia.
His medical historical past included sort 2 diabetes, hypertension, hyperlipidemia, persistent obstructive pulmonary illness, non-small cell lung most cancers and ocular hypertension. He had been adopted by the glaucoma division for a historical past of elevated IOP (highest: 24 mm Hg proper eye, 23 mm Hg left eye) and had elevated corneal thickness on pachymetry in each eyes. He was on latanoprost eye drops in each eyes.
Supply: James T. Kwan, MD, and Lianna Valdes, MD
Examination
Upon examination, the affected person’s imaginative and prescient was 20/200 in the precise eye and 20/50 within the left eye in contrast with a baseline of 20/70 and 20/30, respectively. IOP was regular at 14 mm Hg in each eyes. Pupils had been irregularly formed. The anterior examination was important for 3+ cell with fibrin within the anterior chamber and practically 360° of posterior synechiae in each eyes. There was no proof of keratic precipitates. There was solely a restricted, hazy view to the posterior section. OCT of the macula had poor sign power however was in any other case unremarkable (Determine 1). B-scan ultrasonography demonstrated a flat retina with proof of vitreous particles in each eyes.
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Blurred imaginative and prescient, photophobia
The affected person’s presentation is according to bilateral non-granulomatous acute anterior uveitis.
A radical evaluation of programs and social historical past ought to be taken in sufferers with acute shows of uveitis. The differential is broad, together with infectious, inflammatory, neoplastic and iatrogenic etiologies. Infectious etiologies could embrace syphilis, tuberculosis, herpes simplex virus, varicella-zoster virus, cytomegalovirus, toxoplasmosis and rubella. The affected person’s social historical past was unremarkable, and there was no current report regarding infectious illness involvement. Inflammatory circumstances, similar to HLA-B27-associated uveitis and tubulointerstitial nephritis and uveitis (TINU) syndrome, and post-streptococcal uveitis had been additionally thought-about; nevertheless, the absence of a historical past of rheumatologic circumstances or current systemic sickness makes these diagnoses much less possible. Neoplastic etiologies, similar to lymphoma or metastases, stay a chance given the affected person’s identified analysis of non-small cell lung carcinoma. Lastly, medicines are thought-about a potential etiology within the setting of bilateral acute-onset uveitis. The commonest treatment lessons implicated in uveitis embrace bisphosphonates, sulfonamides, BRAF/MEK inhibitors and immune checkpoint inhibitors. A radical evaluation of this affected person’s treatment record revealed current cessation of pemetrexed and carboplatin along with current initiation of dabrafenib and trametinib for remedy of non-small cell lung most cancers.
Given the broad differential, workup for these sufferers usually contains serum ACE, lysozyme, FTA-Abs, RPR, QuantiFERON Gold, HLA-B27 antigen, urine beta-2 microglobulin, antistreptolysin O titers and a chest X-ray along with a whole blood depend and fundamental metabolic panel. OCT imaging can typically present beneficial insights into the underlying etiology of uveitis and assist determine issues from uveitis, similar to cystoid macular edema or choroidal neovascularization, that will affect administration selections.
Prognosis and administration
Contemplating the historical past of non-small cell lung most cancers and the temporal relationship between initiation of dabrafenib and trametinib and improvement of uveitis, the medical presentation was deemed most according to BRAF/MEK inhibitor-associated uveitis.
The affected person was began on prednisolone acetate drops hourly and cyclopentolate drops twice each day in each eyes to cut back irritation and assist break the posterior synechiae. Additional investigation revealed that the affected person had not too long ago switched his chemotherapeutic routine to dabrafenib and trametinib, as he had been having insupportable nausea whereas on pemetrexed and carboplatin, together with evening sweats, tremulousness, fatigue and dysgeusia inflicting anorexia. It was determined right now to carry his chemotherapeutic routine.
Over the course of the subsequent month, the affected person’s signs principally resolved. Visible acuity improved to twenty/60 in the precise eye and 20/40 within the left eye. There was solely hint anterior chamber cell current in each eyes, and a steroid drop taper was initiated. With important enchancment in signs, a collaborative choice was made per oncology to reinitiate most cancers remedy with pembrolizumab.
Dialogue
Simultaneous acute-onset bilateral anterior uveitis is a uncommon medical presentation that extra regularly impacts younger sufferers and is related to a broad differential (Birnbaum et al.). Most typical etiologies embrace post-infectious (notably poststreptococcal syndrome uveitis), drug-induced and idiopathic uveitis; HLA-B27 positivity is usually related however classically presents with alternating unilateral non-granulomatous anterior uveitis. Though uncommon, different potential causes embrace TINU syndrome and Behçet’s illness. TINU has been related to current use of systemic antibiotics or NSAIDs, whereas Behçet’s usually presents with a attribute shifting hypopyon. Given the large differential for simultaneous acute-onset bilateral anterior uveitis, a complete historical past — together with treatment use and a scientific evaluation of programs — together with an intensive laboratory workup, is essential for correct analysis.
BRAF/MEK inhibitor-associated uveitis is a well-reported entity. These medicines are used to inhibit the MAPK pathway, which in physiological circumstances is vital in cell survival and proliferation (Subbiah et al.). These medicines are indicated for any strong tumor or non-small cell lung most cancers with BRAF V600E+ mutations (Proietti et al.; Gouda et al.), as is the case for our affected person. Frequent systemic opposed results embrace fever, fatigue, diarrhea, hypertension and transaminitis; nevertheless, ocular involvement has additionally been reported. Ocular opposed results particularly embrace bilateral anterior uveitis, dry eye, retinal vein occlusions, cystoid macular edema and/or multifocal serous retinal detachments (Tarim et al.; Dimitriou et al.). Close to uveitis, potential explanations have proposed that BRAF/MEK inhibitors disrupt the blood-retinal barrier and promote the formation of shared epitopes between the choroid and melanocytes, thus enabling an autoinflammatory course of to happen within the eye. The irritation throughout the eye contributes to a prothrombotic setting and explains the noticed elevated danger for vein occlusions in these sufferers (Molero-Senosiain et al.). Ocular floor dryness is attributed to the disruption of regular tissue proliferation, which might extra considerably have an effect on cells with fast turnover, similar to these within the corneal epithelium (Ma et al.).
In sufferers with substantial systemic comorbidities, a multidisciplinary dialogue is important to weigh the dangers of continuation vs. discontinuation of the present systemic remedy. Nevertheless, a stepwise method within the administration of BRAF/MEK inhibitor-associated uveitis may be carried out earlier than contemplating definitive discontinuation of remedy. Proposed remedy methods usually contain topical corticosteroids with cycloplegic brokers, if mandatory. Discontinuation of BRAF/MEK inhibitors is mostly reserved for circumstances with extreme, vision-threatening or refractory uveitis. Ophthalmic opposed occasions related to these therapies are uncommon and most are manageable with native remedies, permitting sufferers to proceed their most cancers remedy with out interruption (Castillejo-Bacerra et al.). Within the case of retinal vein occlusions, everlasting discontinuation of MEK inhibitors has been beneficial (Welsh et al.). Fortuitously, our affected person skilled a fast restoration and was subsequently transitioned to an alternate remedy, chosen on the discretion of the oncology staff, which has not resulted in recurrence of signs. Notably, pembrolizumab, a PD-1 receptor inhibitor additionally related to uveitis, has not led to any ocular issues on this case. Most not too long ago, the affected person was evaluated for cataract surgical procedure and subsequently underwent profitable surgical procedure in the precise eye, with imaginative and prescient bettering to twenty/25.
- References:
- Birnbaum AD, et al. Arch Ophthalmol. 2012;doi:10.1001/archophthalmol.2012.2006.
- Castillejo Becerra CM, et al. Eur J Ophthalmol. 2022;doi:10.1177/11206721221132872.
- Dimitriou F, et al. Eur J Most cancers. 2021;doi:10.1016/j.ejca.2020.11.027.
- Dobrin RS, et al. Am J Med. 1975;doi:10.1016/0002-9343(75)90390-3.
- Gouda MA, et al. Am Soc Clin Oncol Educ E-book. 2023;doi:10.1200/EDBK_404770.
- Ma J, et al. Breast. 2020;doi:10.1016/j.breast.2020.07.009.
- Molero-Senosiain M, et al. Cureus. 2022;doi:10.7759/cureus.28372.
- Proietti I, et al. Cancers (Basel). 2020;doi:10.3390/cancers12071823.
- Subbiah V, et al. Tendencies Most cancers. 2020;doi:10.1016/j.trecan.2020.05.009.
- Tarm B, et al. J Ophthalmic Inflamm Infect. 2023;doi:10.1186/s12348-023-00339-0.
- Welsh SJ, et al. Ther Adv Med Oncol. 2015;doi:10.1177/1758834014566428.
- For extra info:
- Edited by William W. Binotti, MD, and Julia Ernst, MD, PhD, of New England Eye Heart, Tufts College Faculty of Medication. They are often reached at william.binotti@tuftsmedicine.org and julia.ernst@tuftsmedicine.org.
