Describing the clinical and subclinical characteristics of retinal lesions in Lupus patients; assessing the results of treatment of retinal lesions in patients with systemic lupus erythematosus.
1 INTRODUCTION Systemic lupus erythematosus (SLE) is the most common disease in the autoimmune disease group. The disease stands out with diverse lesions in many organs, internal organs, chronic progression over many years, alternating many exacerbations that greatly affect the quality of life of patients even leading to death The ophthalmic manifestations in Lupus can threaten the vision and impair the patient’s life quality, which is also an indicator of advanced systemic disease. In Vietnam, there are currently no reports of eye injuries caused by the pathological process of Lupus, especially the fundus lesions. So we proceed to the topic: “Studying the clinical, subclinical characteristics and treatment of retinal lesions in patients with systemic Lupus erythematosus” with the two following goals: 1. Describing the clinical and subclinical characteristics of retinal lesions in Lupus patients 2. Assessing the results of treatment of retinal lesions in patients with systemic lupus erythematosus NEW CONTRIBUTIONS OF THE THESIS This is the first study in Vietnam on retinal lesions caused by Lupus, assessing the forms of retinal lesions caused by Lupus, the severity of injuries as well as the risk of losing sight of patients. , thereby proposing systematic and periodic eye examinations for patients for early detection and timely treatment of eye lesions caused by Lupus. This study assesses the results of treatment of retinal lesions, thereby proposing a treatment regimen as well as selecting treatment methods appropriate to each morphology and extent of lesions, contributing to preserving the function of vision. awareness for Lupus patients, improving the quality of life for patients as well as reducing the burden on families and society Partly elucidating the mechanism of lesions, the relationship between visceral lesions in Lupus and eye lesions will contribute to improving the effectiveness of treatment coordination between Ophthalmologists and physicians of Clinical Allergy Immunology STRUCTURE OF THE THESIS The thesis is 155 pages long, consisting of the following sections: Introduction (2 pages), Chapter 1: Literature Overview (45 pages), Chapter 2: Research subjects and methods (28 pages); Chapter 3: Research results (32 pages); Chapter 4: Discussion (47 pages); Conclusion (2 pages); Recommendations (1 page). In the thesis, there are 41 tables, 10 charts and 19 photos. There are 102 references (11 documentsin Vietnamese and 91 documents in English). CHAPTER 1 LITERATURE OVERVIEW 1.1. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) 1.1.1. Definitions: Lupus is a disease with multiple organ lesions in which the autoimmune mechanism plays the most important role in the pathogenesis mechanism. It is characterized by the production of autoantibodies against the components of the nucleus of the cell itself, multiorgan lesions, multiple acute progression, alternating with regressions of the disease. Lupus is more common in women, especially in reproductive and working age 1.1.2. The diagnostic criteria for Lupus: According to SLICC (2012) 1.1.3. Assessing the severity of systemic lupus erythematosus: Based on the SLEDAI scale, classified as follows: Mild and moderate disease SLEDAI ≤ 10, severe disease when SLEDAI> 10. 1.1.5. The relationship between the pathological process of Lupus and the patterns of ocular lesions: Ocular legions and immune disorders that form autoantibodies against organs Disorders of coagulation cause vascular complications Reducing blood cell lines causing lesions to retina, optic nerve Glomerular lesions causes hypertension nephrotic syndrome with atherosclerosis and ophthalmic manifestations Autoimmune mechanism of diabetes and ocular lesions Ocular lesions due to the treatment of Lupus with corticoides, synthetic anti malarial drug. 1.2. CLINICAL CHARACTERISTICS OF RETINAL LESIONS IN LUPUS 1.2.1. The morphologies of retinal vascular lesions 1.2.1.1 Retinal Vasculitis: * Retinal Vasculitis without retinal embolism: more common in microcircular lesions, typically with the presence of cotton nodules (824%), retinal hemorrhages, changes in blood vessel shape, common in small arteries. * Retinal Vasculitis with retinal embolism: is a retinal vascular disease due to inflammation of small arteries, arterioles accompanied by occlusive complications, retinal anemia, this is the main and very serious clinical manifestation of the disease, with symptoms such as: nodules cotton, superficial retinal hemorrhage (see 510%), small arterioles (13.2%), clear vascular cages, resident retinal edema or dissemination due to rupture retinal blood barrier. 1.2.1.2 Blockage of large blood vessels of the retina: more rarely, with manifestation of occlusion or total occlusion of the central retinal vein causing severe retinal anemia, very common in the presence of antiphospholipid syndrome (APS). Lupus retinopathy has varying degrees of anemia, and the width of the anemia is proportional to the degree of visual impairment. Vascular occlusion causes severe retinal anemia, which can be accompanied by complications of new neovascularization 1.2.2. The degrees of retinal lesions due to Lupus: consisting of 3 levels Localized retinal ischemia Blockage of large blood vessels causes severe retinal anemia Retinopathy of proliferation 1.2.3. Combined lesions: Choroidal lesions: more common with choroidal anemia Most inflammation lesions in retinal vein occlusion due to Lupus have clearly vitreous Hemorrhagic vitreous is common in cases of complications of neovascular proliferation Macular lesions: common condition is edema and anemia in macular region Rare optic nerve lesions (1%), manifesting edema optic nerve and optic nerve anemia in front or back. 1.3. SUBCLINICAL TESTS Ophthalmoscopy allows the evaluation of specific lesions of inflammation in retinal vein occlusion due to Lupus Fluorescent angiography, optical coherence tomography OCT and ultrasound mode B techniques play an important role in detecting and evaluating retinal lesions and monitoring treatment 1.4. Differential diagnosis: with causes of Retinal Vasculitis in general 1.5. TREATMENT METHODS 1.5.1. Systemic treatment: The main purpose is to suppress immuneacting activities, reducing the concentration of autoantibodies that fight off organs. Corticoides is the firstline treatment option and is the shortest treatment available for due to Lupus systemic vasculitis as well as retinal Vasculitis in the eyes. Corticoides treatment or have severe side effects. Synthetic antimalarial drugs such as Chloroquine, Hydroxychloroquine (HCQ) have the effect of reducing future outbreaks, preventing relapses and the progression of Lupus disease. Other drugs: antiplatelet aggregation drugs, anticoagulants, exchange plasma 1.5.2. Local treatment: The main purpose is to prevent complications caused by embolic condition, contributing to preserving vision for Lupus patients 1.5.2.1. Retina laser: This is the first treatment option for complications of embolism that causes anemic retinopathy due to Lupus. Laser designation according to the degree of anemic retinopathy: Light anemic retinopathy under 2 optic disc area: track Anemic retinopathy weighing over 5 optic disc areas: whole peripheral retina laser to near the temporal arc (PRP) Anemic retinopathy averages from 2 to less than 5 optic disc areas: the laser covers the entire anemic area Retinal neovascularization in peripheral: find the starting position of neovascularization so that the laser then the entire retinal laser region is anemic, in case of neovascularization and optic nerve, the risk of vitreous body hemorrhage must be combined with intraocular injection with Avastin 1.5.2.2. AntiVEGF (Avastin) AntiVEGF drugs are effective in preventing and treating complications of neovascular proliferation of the retina due to Lupus, which inhibits retinal neovascularization and limits the spread of existing neovascularization. Bevacizumab (Avastin) is a monoclonal antibody designated intraocular injection to treat retinal neovascularization, neovascularization and optic nerve complications with a dose of 1.25mg / 0.05ml Indications for injection Avastin in cases: In the case of thrombophlebitis causes severe anemic retinopathy risk of high neovascular proliferation, Neovascularization of optic nerve have a risk of heamorrhagic vitreous Neovascularization of the macular, macular edema 1.5.2.3. Resection of vitreous body Prescription: treatment of proliferation complications, retinal detachment, haemorrhagic vitreous due to neovascularization of optic nerve 1.5.2.4. Other treatments: adapted on the spot The combination of systemic and ophthalmic treatment is the key to reducing serious eye complications, preserving vision function for patients. CHAPTER 2 RESEARCH SUBJECTS AND METHODS 2.1. RESEARCH SUBJECTS Patients coming for outpatient examination at the Examination Department of Bach Mai Hospital and VNIO are diagnosed to identify Lupus according to SLICC 2012 with retinal lesions in the eyes Research period from June 2013 to June 2017 Research location: Examination Department of Bach Mai Hospital and VNIO 2.1.1. Criteria for selecting a patient: Patients diagnosed with Lupus according to SLICC 2012 will be screened for retinal lesions at the eye 2.1.2. Exclusion criteria + Patient has ocular trauma due to previous injury + Patients do not agree to participate in the study + The patient participated in the study at the previous selection 2.2. RESEARCH METHODS 2.2.1. Research design: Clinical intervention, prospective, no control group 2.2.2 Sample size: Applied the formula for calculating sample sizes using WHO sample software p1 p n Z 21 / d2 In which: n is the needed minimum sample size Z (1 /2) =1.96 (95% reliability, =0,05) p = 0.1 (The rate of retinal lesions in Lupus patients is about 10%.) d = 0.1 found n = 34.57 ≈ 35 eyes 2.2.3. Research facilities: including media Serving eye screening Laboratory facilities at VNIO Digital retinal fluorescent angiography machine (Carl Zeiss) Optical coherence tomography machine (OCT 3 Carl Zeiss), Ultrasound B machine Means of treatment of retinal lesions at VNIO Retina laser machine Room for intraocular injection, intraocular injection kit, Avastin medicine Surgical means Subclinical tests of SLE: Conducted at Labo Centers for Allergy Clinical Immunology, Biochemistry and Hematology at Bach Mai Hospital 2.2.4. Steps to conduct the research Research process The patient was diagnosed with Lupus Interview and eye screening Optometry, intraocular pressure prepartial examination fundoscopy If there is a lesions to the fundus Fluorescence angiography Optical coherence tomography (OCT) Bscan ultrasonography Subclinical test of Lupus Research indicators on Lupus status, retinal condition before treatment Systemic treatment combined with ophthalmic treatment Research indicators on retinal condition, eyesight after treatment 2.2.4.1 Interview: All patients were asked to get information Assessing the severity of Lupus according to SLEDAI: Record all body test results, subjective signs at eyes 2.2.4.2 Screening to detect Retinal lesions at the eye Optometry: Snellen vision chart, visual acuity test with corrective lenses Vision results based on ICO report classification Sydney 2002 Convert Snellen vision to logMAR vision table Measurement of intraocular pressure, partial examination Examination of the fundus: by direct ophthalmoscopy, Volk superfield glasses and 3sided mirror glass Forms of Retinal lesions: * Retinal vasculitis: including microcirculation lesions (exudative cottons, retinal hemorrhage), retinal vascular changes, with or without retinal occlusion + Exudative cottons: Assessed based on the number, location and size of the secretion compared to the optic disc area Mild level: when the secretion size is less than 1/4 of optic disc area Moderate level: secretion size from 1/4 to 1/2 area optic disc Severe level: when secretion is large on 1/2 optic disc area + Retinal hemorrhage: assessing the location, morphological form (dot, candle or cloud), size and level of bleeding. According to Wisconsin, bleeding levels include " Mild level: when hemorrhage size is less than 1/4 of optic disc area Moderate level: sized from 1/4 to 1/2 optic disc area Severe level: large hemorrhage on 1/2 optical disc area + Changes in the shape of retinal blood vessels: location of Retinal Vasculitis (in capillaries, arterioles, arteries or central veins of the retina). The levels of change are as follows: Level 1: Blood vessels dilate slightly Level 2: Shrink blood vessels with irregular diameter Level 3: Severe when there is an image of a blood vessel, breaking or changing the direction of the blood vessel + It may be accompanied by vascular lesions causing anemic retinopathy. * Occlusion of the retina: Evaluation of the embolization site, causing corresponding retinal perfusion is observed on fluorescent angiography, may include retinal neovascularization, neovascularization of optic nerve, vitreous hemorrhage, proliferation, retinal detachment contraction + Choroid condition: + Vitreous condition: degree of transparency, cloudiness, hemorrhage vitreous + Macula: Anemia, edema macular region + Status of optic disc: pink, suitable optic disc, concave, atrophic optic disc, neovascularization of optic disc. 2.2.4.3 The subclinical test in the eye * Fluorescent angiography: detected retinal vascular lesions: retinal vasculitis, retinal embolism, anemic retinopathy. + Anemic retinopathy area: o Mild level: anemic area of less than 2 optic disc area o Moderate level: from 2 to less than 5 optic disc area o Severe level: anemic area of more than 5 optic disc areas + Abnormal fluorescence and numerous cases of retinal neovascularization + Other combined lesions such as anemia choroidal, anemia or edema macular * OCT: optical coherence tomography in case of suspected macular region lesions. Measurement of central retinal thickness and macular region. * Ultrasound B: Used in cases where the fundus cannot be used to assess the vitreous, retinal condition. 2.2.4.4 The subclinical test of SLE disease Subclinical results of patients with Lupus include: blood counts, blood biochemistry, coagulation indices, urine tests, proteinuria quantification in 24 hours, tests to detect antibodies against nucleus, antibodies to DsDNA, antibodies to phospholipids, blood pressure and weight values 2.2.4.5 Indications for treatment according to morphology and degree of Retinal lesions * Retinal Vasculitis group: Treated with Bolus Corticoides Without retinal occlusion: monitor If accompanied by embolism: depending on the degree of anemia to specify + Anemic Retinopathy areas of papillae: Laser peripheral peripheral retina close to 2 temporal arcs + In case of a major thrombophlebitis causing severe anemic retinopathy after Bolus corticoides and laser peripheral peripheral retina, it is necessary to appoint intraocular injection Avastin in combination to prevent early neovascular proliferation complications * Simple retinal occlusion group: Firsthand treatment is Laser If there is no complication of neovascular proliferation: laser indicated according to the level of anemic retinopathy: + Anemic Retinopathy areas of papillae: Laser peripheral peripheral 10 retina close to 2 temporal arcs If there are complications of neovascular proliferation: depending on the location of neovascularization to specify treatment + Retinal neovascularization in peripheral laser is close to the starting position of neovascularization and the retinal area is anemic. Postpartum retinal neovascularization requires intraocular injection of Avastin + Neovascularization of optic nerve: Whole peripheral retina laser is closer to the 2 temporal arteries, if neovascularization of optic nerve are not dissipated or there is a risk of vitreous body hemorrhage requiring intraocular injection Avastin + In case of examination, there is a complication of proliferation causing retinal detachment requiring surgery 2.2.5. Result evaluation 2.2.5.1 According to research indicators 2.2.5.2 Evaluation of specific results * Functional results: Subjective signs of the patient * Functional results Eye sight: Evaluating the changes in vision and visual acuity results after treatment Good results: clinically the level of vision remains the same or increases Bad results: clinically impaired vision or vision loss * Entity results Ophthalmoscopy Good results: Retinal vasculitis reduced, no new neovascularization, no vitreous hemorrhage, old regressing neovascularization Bad results: Recurrent vasculitis retinal condition, new neovascularization, , vitreous body hemorrhage, retinal proliferation, complications of retinal detachment Fluorescent angiography Good results: No new anemic area. The old anemic area has been replaced by laser scarring, no new neovascularization or neovascularization remains, but regression is reduced Bad results: New areas of retinal anemia appear, new neovascularization in retina and papillae Optical coherence tomography (OCT): Macular edema after treatment has Good results: when macular region retinal thickness is reduced Bad results: when macular region retinal thickness increases 13 eyes (n=52) 12 14 26 % 23,1 26,9 50 No retinal embolism With retinal occlusion Retinal occlusion merely does not cause vasculitis 3.2.2.2 Trauma positions of fundus 3.2.2.3 Merocrine secretion: found in 22 eyes Table 3.10: Levels of merocrine secretion and forms of Retinal lesions Level of Lesion forms Total merocrine n = 22 Retinal Vasculitis Simple secretion retinal No retinal With retinal embolism embolism occlusion Mild 2 (9,1%) 1 (4,5%) 1 (4,5%) 4 (18,1%) Moderate 2 (9,1%) 1 (4,5%) 3 (13,6%) Severe 3 (13,7%) 12 (54,6%) 15 (68,3%) 7 (31,9%) 14 (63,6%) 1 (4,5%) 22 (100%) Total Retinal Vasculitis 3.2.2.4 Retinal hemorrhage: found on 23 eyes Mild and moderate retinal hemorrhage makes up the majority of 86.9%. The rate of retinal hemorrhage is high in the group of Retinal Vasculitis 3.2.4. Subclinical characteristics: 3.2.3.1 Retinal Vasculitis status on fluorescent angiography: Table 3.12: Retinal vascular transformation according to lesion forms The degree Lesion forms of retinal Total Retinal Vasculitis Simple vascular n=26 retinal No retinal With retinal embolism embolism changes occlusion Mild 8 (30,8%) 2 (7,7%) 10 (38,5%) Moderate 4 (15,4%) 6 (23,1%) 10 (38,5%) Severe 6 (23%) 6 (23%) 12 (46,2%) 14 (53,8%) 26 (100%) Total Artery Table 3.13: Trauma position of retinal vasculitis Position Number of eyes with retinal vasculitis (n = 26) Small size (arterioles) 22 Rate % 84,6 14 Vein Large size (branches, central arteries of the retina) Small size Large size (branches, central veins of the retina) 10 38,5 0 7,7 Capillary 15 57,7 3.2.3.2 Trauma position clogs retinal blood vessels Table 3.15: Trauma position of retinal occlusion Position Number of eyes with Rate % retinal embolism (n=40) Small size (arterioles) 27 67,5 Artery Large size (branches, central 18 45 arteries of the retina) Small size 0 Vein Large size (branches, central veins of the retina) Capillary 22 55 3.2.3.3 The condition of anemic retinopathy in the research team: There were 39 eyes showing anemic retinopathy, in which moderate and severe anemic retinopathy accounted for the majority of cases 94.9%. 3.2.3.4 Retinal neovascularization, optic nerve before treatment in studied group The rate of neovascularization seen in the studied group is 30.8%, the proliferative retinopathy seen in eyes accounts for 13.5% All cases of neovascularization, retinopathy of proliferation at baseline were in the simple occlusive group without these lesions in the retinal vasculitis group Table 3.18: Neovascularization and Anemic Retinopathy degree Degree of anemia Neovascularization Total Võng mạc Optic nerve 0 Mild: 5 S optic nerve 14 (87,5%) 2 (12,5%) 16 (100%) Total 3.2.4. Other combined lesions 15 3.2.4.1 Vitreous body: In all forms of retinal lesions, vitreous body in the majority accounted for 84.6% 3.2.4.2 Choroid Table 3.20: Choroidal lesions trong studied group Choroidal lesions Anemia choroidal Secretion retinal detachment Central retinal vitiligo Pigment epithelial lesion Total Lesion forms Total Retinal Simple retinal Vasculitis occlusion 12 (66,7%) 2 (11,1%) 14 (77,8%) 1 (5,5%) 1 (5,5%) 0 3 (16,7%) 3 (16,7%) 16 (88,9%) 2 (11,1%) 18 (100%) 3.2.4.3 Optic nerve: No optic nerve inflammation Atrophie of optic nerve accounts for 62.5%. Neovascularization of optic nerve found on 2 cases. 3.2.4.4 Macula Table 3.22: Macular lesions trong studied group Macular lesions Lesion forms Total Retinal Simple retinal Vasculitis occlusion 9 (33,3%) 2 (7,4%) 11 (40,7%) 7 (25,9%) 1 (3,7%) 8 (29,6%) 2 (7,4%) 5 (18,5%) 7 (25,9%) 1 (3,7%) 1 (3,7%) Anemia macula Macular edema Thin central retinal atrophy Neovascularization under the retina Macular poisoning due to drugs 0 18 (66,7%) 9 (33,3%) 27 (100%) Total 3.2.5 Functions: 3.2.5.1. Vision before treatment of studied group The poor vision rate 20/200 accounts for up to 50% of cases before treatment 3.2.5.2 Grouping of vision before treatment lesion forms and degree of anemia 3.3. TREATMENT RESULTS 3.3.1. Results of treatment in the Retinal Vasculitis group: 16 3.3.1.1 Initial treatment methods Table 3.26: Initial treatment methods in the group of Retinal Vasculitis Method Number of eyes Rate (n=26) Bolus 12 46,1 Bolus+laser 30,8 Bolus+laser+Avastin injection 23,1 3.3.1.2 Entity results: In vasculitis group, the rate of encountering merocrine secretion, hemorrhage, retinal vasculitis was high before treatment, this rate gradually decreased after Bolus treatment and ended at months after treatment There were no cases of neovascularization or retinopathy of proliferation at the time of examination in this form 3.3.1.3 Complementary treatment of complications of neovascular proliferation Table 3.29: Complementary treatment in the Retinal Vasculitis group After 1 After 3 After 6 After 9 After 12 Last Forms Methods month months months months months time Vasculitis Bolus 0 0 with retinal Laser 13 10 0 occlusion Avastin 3 0 injection Surgery 1 3.3.1.4 Treatment methods Method Bolus Bolus + laser Bolus + laser + Avastin ịnection Bolus + laser + Surgery Bolus + laser + Avastin + Surgery 3.3.1.5 Functional results Number of eyes 12 Rate 46,2 7,7 15,4 3,8 26,9 17 Chart 3.4: Vision changes of Retinal Vasculitis group Vision improved at 1 month after Bolus however at 39 months vision was lesionsd more. There were no significant differences between the mean log MAR visual value at the end of the followup compared to before treatment. Retinal Vasculitis group had 46.2% of cases with vision> 20/200 after treatment 3.3.2. Treatment results in the Simple retinal occlusion group 3.3.2.1 Initial treatment methods Table 3.30: Initial treatment methods of retinal occlusion Methods Number of eyes Rate (n=26) Laser 15 57,7 Laser + Avastin injection 11,5 Avastin injection 7,7 Avastin injection+Vitreous body resection 3,8 Vitreous body resection 19,2 3.3.2.2 Entity results The Simple retinal occlusion group without the expression of retinal vasculitis had a high rate of anemic retinopathy before treatment of 96.2%, which gradually decreased and ended at 12 months with prophylaxis with retina laser The pretreatment neovascularization status of this group was 61.5%. 26.9% of cases with retinopathy increased during the examination. There was no new neovascularization at 12 months after treatment. 3.3.2.3 Complementary treatment in the Simple retinal occlusion group: few 3.3.2.4 Treatment methods Method Number of eyes Rate Laser 14 53,8 Laser + Avastin ịnection 11,5 18 Laser + Surgery Avastin iniection Avastin injection + Surgery Surgery 1 3,8 3,8 7,7 19,2 3.3.2.5 Functional results Vision improved gradually over time of followup in the Simple retinal occlusion group, there was a statistically significant difference when assessed at the followup of 6 months compared to 3 months after treatment. Vision after treatment of this group improved significantly compared to before treatment Only 7.7% of cases had posttreatment vision in this group 20/200. Chart 3.6. Visual changes of the Simple retinal occlusion group 3.3.3 Evaluating the effectiveness of treatment in 2 groups 3.3.3.1. Vision results in 2 groups There was no difference in visual acuity of the two groups; however, the percentage of patients with postoperative visual acuity> 20/200 in 2 groups had a statistically significant difference with p 20/200 after treatment in the thromboembolism group alone was 76.9% higher than that in the vasculitis group 3.3.3.2. Success rate in 2 groups Table 3.36: Success rate in 2 groups Completely successful Group of retinal vasculitis Group of retinal occlusion P 9 (34,6%) 7 (26,9%) >0,05 19 Partially successful Failed 15 (57,7%) 19 (73,1%) 2 (7,7%) 0 0,05 complications 3.3.4. General treatment results of studied group 3.3.4.1 Mechanical capacity: The symptoms of blurred vision improved in some cases after treatment, the visual acuity ratio reached> 20/200 after treatment in studied group was 61.5%, there was no case of complete vision loss 3.3.4.2 Function: Eyesight Chart 3.8: Comparison before and after treatment by vision group The results of vision after treatment are good if increase or stay the same, accounting for 69.3%, vision loss after treatment accounts for 30.7% The average value of logMAR vision varies according to the followup time, when there are differences in the 6month and 3month intervals between the average decrease in visual acuity. Comparison before treatment and end of monitoring had statistically significant improvement in visual acuity p 20/200 accounted for 83.3% In contrast, in the vasculitis group associated with thrombosis causing anemic retinopathy, up to 50% of cases have visual lesions