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 goa
Trang 1Systemic lupus erythematosus (SLE) is the most common disease inthe autoimmune disease group The disease stands out with diverse lesions inmany organs, internal organs, chronic progression over many years, alternatingmany exacerbations that greatly affect the quality of life of patients evenleading to death
The ophthalmic manifestations in Lupus can threaten the vision andimpair the patient’s life quality, which is also an indicator of advanced systemicdisease In Vietnam, there are currently no reports of eye injuries caused by thepathological 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 andperiodic eye examinations for patients for early detection and timely treatment
of eye lesions caused by Lupus This study assesses the results of treatment ofretinal lesions, thereby proposing a treatment regimen as well as selectingtreatment 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 onfamilies and society Partly elucidating the mechanism of lesions, therelationship between visceral lesions in Lupus and eye lesions will contribute toimproving the effectiveness of treatment coordination betweenOphthalmologists 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: Researchsubjects and methods (28 pages); Chapter 3: Research results (32 pages);Chapter 4: Discussion (47 pages); Conclusion (2 pages); Recommendations (1page) In the thesis, there are 41 tables, 10 charts and 19 photos There are 102references (11 documentsin Vietnamese and 91 documents in English)
Trang 2CHAPTER 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 pathogenesismechanism It is characterized by the production of autoantibodies against thecomponents of the nucleus of the cell itself, multi-organ lesions, multiple acuteprogression, 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 withatherosclerosis and ophthalmic manifestations
- Autoimmune mechanism of diabetes and ocular lesions
- Ocular lesions due to the treatment of Lupus with corticoides, synthetic malarial drug
anti-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 (8-24%),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 byocclusive complications, retinal anemia, this is the main and very seriousclinical manifestation of the disease, with symptoms such as: nodules cotton,superficial retinal hemorrhage (see 5-10%), small arterioles (13.2%), clearvascular cages, resident retinal edema or dissemination due to rupture retinal
Trang 3blood 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 causingsevere retinal anemia, very common in the presence of antiphospholipidsyndrome (APS) Lupus retinopathy has varying degrees of anemia, and thewidth of the anemia is proportional to the degree of visual impairment.Vascular occlusion causes severe retinal anemia, which can be accompanied bycomplications 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 clearlyvitreous Hemorrhagic vitreous is common in cases of complications ofneovascular proliferation
- Macular lesions: common condition is edema and anemia in macular region
- Rare optic nerve lesions (1%), manifesting edema optic nerve and optic nerveanemia 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, opticalcoherence tomography- OCT and ultrasound mode B techniques play animportant role in detecting and evaluating retinal lesions and monitoringtreatment
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 immune-acting
activities, reducing the concentration of autoantibodies that fight off organs.Corticoides is the first-line treatment option and is the shortest treatmentavailable for due to Lupus systemic vasculitis as well as retinal Vasculitis in theeyes Corticoides treatment or have severe side effects Synthetic anti-malarialdrugs such as Chloroquine, Hydroxychloroquine (HCQ) have the effect ofreducing future outbreaks, preventing relapses and the progression of Lupusdisease Other drugs: anti-platelet aggregation drugs, anticoagulants, exchange
Trang 41.5.2 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 averages from 2 to less than 5 optic disc areas: thelaser covers the entire anemic area
- Anemic retinopathy weighing over 5 optic disc areas: whole peripheralretina laser to near the temporal arc (PRP)
- Retinal neovascularization in peripheral: find the starting position ofneovascularization so that the laser then the entire retinal laser region isanemic, in case of neovascularization and optic nerve, the risk of vitreousbody hemorrhage must be combined with intraocular injection withAvastin
1.5.2.2 Anti-VEGF (Avastin)
Anti-VEGF drugs are effective in preventing and treating complications ofneovascular proliferation of the retina due to Lupus, which inhibits retinalneovascularization and limits the spread of existing neovascularization.Bevacizumab (Avastin) is a monoclonal antibody designated intraocularinjection to treat retinal neovascularization, neovascularization and optic nervecomplications with a dose of 1.25mg / 0.05ml
Indications for injection Avastin in cases:
- In the case of thrombophlebitis causes severe anemic retinopathy risk ofhigh 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 reducingserious eye complications, preserving vision function for patients
Trang 5CHAPTER 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 toSLICC 2012 with retinal lesions in the eyes
- Research period from June 2013 to June 2017
- Research location: Examination Department of Bach Mai Hospital andVNIO
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
d
p p Z
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 Bmachine
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
Trang 62.2.4 Steps to conduct the research
Research process
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 ConvertSnellen vision to logMAR vision table
- Measurement of intraocular pressure, partial examination
- Examination of the fundus: by direct ophthalmoscopy, Volk superfield glassesand 3-sided mirror glass
Forms of Retinal lesions:
Systemic treatment combined with ophthalmic treatment
Research indicators on retinal condition,
eyesight after treatment
Research indicators on Lupus status, retinal condition
before treatment
The patient was diagnosed with Lupus
Interview and eye screening.
Optometry, intraocular pressure - pre-partial examination - fundoscopy
If there is a lesions to the fundus
Fluorescence
angiography tomography (OCT)Optical coherence ultrasonographyB-scan Subclinical test of
Lupus
Trang 7* 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 thesecretion 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 levelsinclude "
- 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 ofchange 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 orchanging 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, mayinclude retinal neovascularization, neovascularization of optic nerve, vitreoushemorrhage, proliferation, retinal detachment contraction
+ Choroid condition:
+ Vitreous condition: degree of transparency, cloudiness, hemorrhagevitreous
+ 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
Trang 8+ Abnormal fluorescence and numerous cases of retinal neovascularization+ Other combined lesions such as anemia choroidal, anemia or edemamacular
* 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, bloodbiochemistry, coagulation indices, urine tests, proteinuria quantification in 24hours, tests to detect antibodies against nucleus, antibodies to Ds-DNA,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 <2 areas of papillae: monitoring
+ Anemic Retinopathy from 2-5 areas of papillae: Laser covered anemic area+ Anemic Retinopathy> 5 areas of papillae: Laser peripheral peripheralretina close to 2 temporal arcs
+ In case of a major thrombophlebitis causing severe anemic retinopathyafter Bolus corticoides and laser peripheral peripheral retina, it is necessary toappoint intraocular injection Avastin in combination to prevent earlyneovascular proliferation complications
* Simple retinal occlusion group: First-hand treatment is Laser
- If there is no complication of neovascular proliferation: laser indicatedaccording to the level of anemic retinopathy:
+ Anemic Retinopathy <2 areas of papillae: monitoring
+ Anemic Retinopathy from 2-5 areas of papillae: Laser covered anemic area+ Anemic Retinopathy> 5 areas of papillae: Laser peripheral peripheralretina close to 2 temporal arcs
- If there are complications of neovascular proliferation: depending on thelocation of neovascularization to specify treatment
+ Retinal neovascularization in peripheral laser is close to the startingposition of neovascularization and the retinal area is anemic Postpartum retinalneovascularization 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
Trang 9+ In case of examination, there is a complication of proliferation causingretinal 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
Fluorescent angiography
- Good results: No new anemic area The old anemic area has been replaced bylaser scarring, no new neovascularization or neovascularization remains, butregression is reduced
- Bad results: New areas of retinal anemia appear, new neovascularization inretina 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
Assess complications during eye treatment
* Final treatment results for Retinal lesions due to Lupus: evaluated
according to two criteria:
1 Preserving and improving the eyesight
2 Preventing the complications
* General results of the treatment process
- Completely successful: When all of the following conditions are met:
+ Vision is preserved or increased compared to before treatment
+ No new neovascularization, regressing old neovascularization, nohemorrhage vitreous, no new anemic retinopathy area, anemic area replaced bylaser scar
- Partially successful
Trang 10+ Vision is preserved or reduced without losing sight
+ New neovascularization, vitreous body hemorrhage, new anemic areaappeared, requiring additional treatment There were no serious complications
of embolic condition of retina such as: vitreous proliferation, retinaldetachment There is no glaucome neovascularization
+ There are complications of treatment process in the eyes but not theserious complications
- Failed: When one of the following conditions is met:
+ Vision loss
+ Severe complications of retinal occlusion: severe vitreous bodyproliferation causing retinal detachment, loss of function
+ Glaucome neovascularization
+ There are severe complications of the treatment process
2.2.6 Data processing methods
- The research data is processed on a computer with SPSS 15.0 software andcleaned before the processing
CHAPTER 3 RESEARCH RESULTS 3.1 CHARACTERISTICS OF STUDIED PATIENT GROUP: 31 PATIENTS 3.1.1 Gender: The male/female ratio is very different, female patients account
for 87.1%, male only 4 patients account for 12.9%
3.1.2 Age at the examination
Chart 3.2: Age of patients at the examination
3.1.3 Age at the onset of Lupus
Most had an early onset of illness, 80.6% of Lupus patients had Retinal lesionsonset before age 30
3.1.4 Systemic lesions of the research team
Trang 11The common manifestations are new rash, inflammation and arthritis painaccounting for 64.5% The manifestations of nerve and mental lesions wereencountered with the rate of 25.8% Kidney lesions in 22.5% of cases.
3.1.5 Test variations
Increased triglycerides account for 50% of cases The proportion of patientswith positive anti-nuclear antibodies in the study group was 35.5%, antibodies
to Ds-DNA positive in 25.8% of cases
3.1.6 Severe level of Lupus
Table 3.5: Severe level of Lupus
Average SLEDAI score 17,23 ± 4,87 min 0 max 30 pointsRate of patients with SLEDAI score> 10 96,8%
Average duration of Lupus 5,19 ± 5,11 min 0 max 25 years Rate of patients having treatment
period> 1 year
87,1%
3.2 CLINICAL AND SUBCLINICAL CHARACTERISTICS, OF RETINAL LESIONS DUE TO LUPUS
3.2.1 Functional symptoms: Blurred vision accounted for 94.2%, 5.7%.
There was no complaint about eyes
3.2.2 Clinical characteristics
3.2.2.1 Retinal lesions forms
Table 3.8: Forms of Retinal lesions
Forms of Retinal lesions Number of
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
retinal occlusion
No retinalembolism
With retinalembolism
Trang 12hemorrhage makes up the majority of 86.9% The rate of retinal hemorrhage ishigh 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
Retinal Vasculitis Simple
retinal occlusion
No retinalembolism
With retinalembolism
Table 3.13: Trauma position of retinal vasculitis
retinal vasculitis (n = 26)
Rate
%
Artery
Large size (branches, central
Vein
Large size (branches, central
3.2.3.2 Trauma position clogs retinal blood vessels
Table 3.15: Trauma position of retinal occlusion
retinal embolism (n=40)
Rate %
Artery
Large size (branches, central
Vein
Large size (branches, central
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%