The full range of ophthalmological clinical manifestations in systemic lupus erythematosus

Abstract

Purpose: To determine the full range of ophthalmological clinical manifestations in systemic lupus erythematosus (SLE) and to compare the systemic features associated with them.

Methods: Files of 13 patients with ocular SLE (n = 20 eyes) diagnosed as per the American College of Rheumatology (ACR) 2012 revised criteria were retrospectively reviewed.

Results: The following clinical manifestations were found: keratoconjunctivitis sicca (n = three patients), anterior uveitis associated with an inflammatory pseudo-tumor orbital mass (n = one patient, one eye), episcleritis and periorbital edema (n = one patient, two eyes), posterior scleritis (n = one patient, two eyes), bilateral papillary edema in the context of idiopathic intracranial hypertension (n = one patient, one eye), inflammatory optic neuritis (n = one patient, one eye), and lupus retinopathies with varying degrees of capillary occlusions mainly arteriolar (n = seven patients, 13 eyes) and larger arteries or veins (retinal arteries occlusions and retinal veins occlusions) (n = one patient, two eyes). Some patients presented with combined ophthalmological manifestations.Systemic SLE was discovered by its ophthalmic manifestation in three cases (23%) and was previously known in the other 10 cases (77%). On average, ocular symptoms were seen 8 years after the initial diagnosis of SLE. Other systemic SLE disorders included cutaneous disorders (77%), joint disorders (38%), central nervous system (CNS) disorders (23%), renal disorders (38%), and oral ulcers (23%).Treatment of the ophthalmic system manifestations of lupus included local steroid therapies along with systemic immunosuppression.The most common laboratory ACR criteria were: high levels of antinuclear antibodies (ANA) (100%), positive anti-Sm (64%), anti-dsDNA (27%), low complement levels (27%), and positive antiphospholipid (APL) antibodies (18%).

Discussion: SLE activity in the ophthalmic system is characterized by its functional severity and the range of involvement can be categorized by anatomical involvement: presence of anterior uveitis, episcleritis, scleritis, periorbital edema, posterior uveitis with retinal vascular ischemia, or papillary edema. Not currently part of the diagnosis criteria of the SLE ACR given its rarity, the ocular localization of the pathology led to the diagnosis of SLE in three cases; thus, developing a greater understanding of ocular lupus may help in identifying and treating systemic manifestations of lupus earlier.

Keywords: Lupus retinopathy; idiopathic intracranial hypertension; lupus; ocular lupus; optic neuritis; posterior scleritis; uveitis; uveitis (MeSH).

Figure 1

Case number 2. External photograph of a 56-year old-female with a medical history of SLE and Sjogren disease that consulted for keratoconjunctivitis sicca, she also complained of polyarthralgias fatigue, oral ulcers and photosensitivity. Ophthalmic exam showed bilateral periorbital edema (blue arrows), and diffuse anterior scleritis (yellow asterisks). At the time of eye presentation, she had been on oral MTX 15 mg weekly combined with 13 mgs of prednisone and belimumab infusions since the past two years.

Figure 2

Case number 3. Optos fundus photos and wide field fluorescein angiography of a 61-year-old female with combined BRVO and BRAO due to mixed connective polyautoimmune SLE negative for antibodies for antiphospholipid syndrome but positive anti-RNP and meningo-encephalitis. (A) Wide view shows absence of vitritis with sheathing of both veins and arterioles. (B) close up that clearly shows sheathing from both veins (arrowheads) and arterioles (red arrows), asterisks show both veins and arterioles that are totally occluded with cotton-wool spots. (C) Intermediate phase FA shows sectoral lack of perfusion superotemporally (yellow dotted circle), with both arteriole (red arrow) and vein (blue arrow) showing lack of flow. (D) Late phase FA that shows staining of the veins compatible with periphlebitis (arrowhead) and partially occluded arteriolar flow proximally (yellow arrow) and distally (red arrow). The patient was treated with sectoral PRP following a period of eye quiescence.

Figure 3

Case number 7. Multimodal imaging of a 48-year-old female with polyarthralgias, diffuse alopecia, ulceration of the hard palate, dyspnea, proteinuria subsequently diagnosed as class-III lupus nephritis, hypergammaglobulinemia and positive anti-Smith antibodies that presented to the ED with acute onset vision loss of the right eye following a biopsy of an axillary lymph node that demonstrated mixed lympho-plasmocytic proliferation compatible with florid systemic lupus. She had been on IV CYC, and oral MMF prior to the ophthalmic manifestations. (A) Fundus photograph shows macular ischemia with inferior hemorrhage and pale looking retina. (B) Late phase FA shows multiple pinpoint areas of leakage with a large area of nonperfusion temporally. (C) OCTA clearly shows lack of blood flow temporal to the fovea. Due the severe retinal ischemia the patient was treated with 1000 mg IV methylprednisolone initially, multiple intravitreal triamcinolone and anti-VEGF injections were needed shortly thereafter due to recurrent vitreous hemorrhages, and the addition hydroxychloroquine was required for further control of intraocular signs of active disease.

Figure 4

Case number 8. Multimodal imaging of a 20-year-old female from the Middle East with a diagnosis of mixed connective tissue disease following positive anti-dSDNA, anti-Smith, anti-RNP and anti-nucleosome antibodies and clinical signs that included oral ulcerations, polyarthralgia, malar rash squamous erythema of the ears and proteinuria diagnosed as extra-membranous lupus glomerulonephritis type V. She presented to the clinic with acute worsening of vision bilaterally. (A) Fundus photo of the right eye and (B) left eye show dense vitreous hemorrhage, vasculitis and tractional membranes. (C) Fundus photo of the right eye and (E) left eye following treatment with PPV, EL and SO. The left eye suffered from recurrent vitreous hemorrhage despite surgical interventions, which can be seen centrally and superiorly. (D) Wide field FA of the right eye with superior and central lack of perfusion, compatible with extensive macular ischemia. She was treated systemically with steroids, MMF and Rituximab.

Figure 5

Case number 11. Fundus photographs of a 39-year-old female with SLE and chronic hydroxychloroquine use for 14 years. (A) There is Frisen grade 1 papilledema of the right eye and (B) Frisen grade 2 papilledema of the left eye. A negative MRI and increased cranial pressure yielded the diagnosis if IIH. Papilledema resolved following treatment with oral acetazolamide (C, D).

Figure 6

Case number 12. Multimodal imaging of a 37-year-old woman with obstetric and thrombotic antiphospholipid syndrome, and clinical signs cutaneous-articular lupus associated with pulmonary embolism quiet on oral 7.5mg of prednisone. She initially complained of decreased visual acuity of the left eye following a period of severe anxiety. (A) FA of the right eye shows multiple pinpoint areas of staining and a central hypofluorescent area compatible with a serous detachment. (B) OCT show thickened serous detachment compatible with posterior scleritis. Systemic mycophenolate mofetil allowed for the control of ophthalmic and systemic symptoms with resolution of serous detachment on SD-OCT (C).

Figure 7

Case number 13. Multimodal imaging of a 77-year-old-female with a positive ANA, C3 and C4 SLE along with leukopenia. She presented with acute left eye vision loss and superior altitudinal defect despite being on oral prednisone. Fundus photo of the right (A) and Left eye (B) show a normal looking right optic nerve but a pale and atrophic left optic nerve. FA of the right (C) and (D) left eye show normal circulation without delays or leaks, ruling out giant cell arteritis or other vascular causes for the vision loss. The guided progression analysis (GPA) of the right (E) and left eye (F) shows progressive decline in the retinal nerve fiber layers of the left eye, compatible with atrophy.