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Nghiên cứu sử dụng thuốc bevacizumab tiêm nội nhãn phối hợp cắt dịch kính điều trị bệnh võng mạc đái tháo đường giai đoạn tăng sinh có biến chứng xuất huyết dịch kính tt tiếng anh

MINISTRY OF EDUCATION AND TRAININGMINISTRY OF HEALTH

HA NOIMEDICALUNIVERSITY

NGUYEN DIEU LINH

STUDY ON USING INTRAVITREAL BEVACIZUMAB
INJECTION AND VITRECTOMY IN THE TREATMENT
OF VITREOUS HEMORRHAGE COMPLICATION DUE
TO PROLIFERATIVE DIABETIC RETINOPATHY

Major : OPHTHALMOLOGY
Code : 62720157

MEDICAL DOCTOR DISSERTATION SUMMARY

HANOI - 2019


THE DISSERTATION IS COMPLETED AT
HANOI MEDICAL UNIVERSITY


Scientific guidance:
Professor Do Nhu Hon

Reviewer 1: Associate professor Tran Thi Nguyet Thanh
Reviewer 2: Associate professor Hoang Nang Trong
Reviewer 3: Associate professor Nguyen Van Dam

The dissertation presented to the Board of Ph.D dissertation at
University level at Hanoi Medical University.
At date . month year 2019.

The dissertation can be found at:
- National Library of Vietnam
- Library of Hanoi Medical University


LIST OF PUBLIC SCIENTIFIC WORKS
RELATED TO THE DISSERTATION

1. Nguyễn Diệu Linh, Đỗ Như Hơn, (2015), “ Evaluation of
treatment results for vitreous hemorrhage in diabetic
retinopathy after 1 year by intravitreal Avastin injection in
combination with vitrectomy”, Vietnamese Journal of
Ophthalmology,vol.38, p:37-43.

2. Nguyễn Diệu Linh, Nguyễn Thị Nhất Châu, Đỗ Như Hơn,
(2015), “ The effectiveness of intravitreal Avastin injection as
an adjunct to vitrectomy in the management of diabetic
vitreous hemorrhage”, Journal of Practical Medecine, N0
987, November, p:95-98


4
INTRODUCTION
Diabetic retinopathy is one of the most prevalent and severe
ocular disorders, which is a major cause of adult blindness. Vitreous
hemorrhage ( VH) is a common complication of proliferative diabetic
retinopathy ( PDR). Vitrectomy is a predominant treatment for
proliferative diabetic retinopathy. The incidence of postoperative


vitreous hemorrhage after vitrectomy is 20%-60%.
Bevacizumab (Avastin) is a recombinant humanized
monoclonal IgG1 antibody that inhibits human vascular endothelial
growth factor (VEGF). Bevacizumab can induce regression of retinal
neovascularization in patients with diabetes; therefore, it was suggested
that a presurgical administration of intravitreal bevacizumab ( IVB)
may reduce intraoperative bleeding during vitrectomy in PDR.
Recently, numerous studies have reported clinical outcomes of
intravitreal bevacizumab as an adjunct to vitrectomy in the management
of proliferative diabetic retinopathy.
In Vietnam, there are no studies that have been performed. Therefore,
the study named " Study on using intravitreal Bevacizumab injection
and vitrectomy in the treatment of vitreous hemorrhage complication
due to proliferative diabetic retinopathy” is conducted with the aims of:
1.To evaluate the effect of intravitreal bevacizumab ( IVB) injection
before vitrectomy in the management of vitreous hemorrhage
complication associated with PDR.
2.To analyse some associated factors with the results.
NEW CONTRIBUTION OF THE THESIS
- Intravitreal Bevacizumab injection and vitrectomy in the treatment of
vitreous hemorrhage due to proliferative diabetic retinopathy help to
limit intraoperative and postoperative complications, improve visual
acuity and anatomical results.
- Systemic factors, complications during surgery do not affect treatment
results. Complications after surgery, additional surgery affect the
outcome of treatment.
STRUCTURE OF THE THESIS
The thesis consists of 139 pages: Introduction (2 pages), Overview
(36 pages), subjects and methods (24 pages), Results (28 pages),
Discussion (46 pages), Conclusion (2 pages), Recommendation (1


5
page). New contribution (1 page). The thesis consists of 32 tables, 6
charts, 5 pictures, appendix and list of patients.
CHAPTER 1
OVER VIEW
1.1. DIABETIC RETINOPATHY
1.1.1. Epidemiology of diabetic retinopathy: Diabetic retinopathy
( DR) usually occurs after 5 years of having diabetes. After 15 years and
20 years more than 50% and most of diabetic patients have retinopathy,
respectively
1.1.2.Pathophysiology of diabetic retinopathy: metabolic changes at
the molecular level leading to endothelial cell dysfunction, basement
membrane thickening, endothelial cell and pericyte loss cell changes.
Those abnormalities contribute permeability changes, retinal occlusion,
formation retinal hypoxia, which stimulates endothelial, pericyte and
retinal
pigment
epithelium
to
produce
VEGF
causing
neovascularization.
1.1.3.Clinical features of diabetic retinopathy
1.1.3.1. Clinical findings: capillary closure, retinal occlusion, retinal
hypoxia, neovascularization. New vessels develope on the surface of
retina or optic disc, create a widespread neovascular network that can
cause complications of vitreous hemorrhage, tractional retinal
detachment and neovascular glaucoma.
1.1.3.2.Classification of DR: According to Alfédiam’s classification
* Non-proliferative diabetic retinopathy: mild, moderate, severe.
* Proliferative diabetic retinopathy: mild, moderate, severe and
complications.
* Diabetic macular retinopathy: focal, diffuse, cyst, tractional macular
edema.
1.1.3.3.Complications of PDR
*Vitreous hemorrhage: The neovascular tissue grows within the outer
cortical vitreous and associate with fibrous tissue proliferation. Traction
due to posterior vitreous detachment lead to vitreous hemohhrage.


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Classification of vitreous hemohhrage according to MR Romano: Grade
0( no hemohhrage, can see fundus clearly in detail), grade 1 (mild
hemorrhage, can see fundus), grade 2 (moderate hemorrhage, can not
see the fundus except the disc), grade 3 (severe hemorrhage, unable to
see the fundus).
*Tractional retinal detachment: Neovascular and fibrous tissue
adhering to the posterior hyaloid membrane shrink the retina leading to
retinal detachment, possibly with retinal tearing.
* Neovascular glaucoma: due to response to hypoxia, VEGF diffuses
to the anterior chamber, causing neovascular on iris and anterior
chamber angle.
1.1.4.Therapies
1.1.4.1.Systemic treatment: Treat diabetes, hypertension and kidney
disease.
1.1.4.2.Panretinal laser photocoagulation: Do laser photocoagulation at
peripheral region to decrease VEGF, thereby reducing neovascularization
1.1.4.3.Anti- VEGF
*Pegaptanip: connect to VEGF-A 165 branch.
*Ranibizumab: connect to all kinds of VEGF.
*Aflibercept: connect to VEGF-A, VEGF-B andplatelet growth factor.
*Bevacizumab ( Avastin): is a monoclonal immunoglobulin,
combining VEGF through 2 antigen-binding sites.
1.1.4.4.Vitrectomy
*Purpose: Removing vitreous , dissecting and removing fibrous
membrane to reattach retina, doing laser photocoagulation to prevent
neovascular.
*Indications: severe vitreous hemorrhage / fibrovascular membrane /
traction macular detachment / traction retinal detachment with retinal tear.
*Technique: vitrectomy from the center to the periphery, making
posterior vitreous detachment
then segment the fibrovascular
membrane by separating them from the retinal surface, re-attach retina,


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laser photocoagulation, using temponade. Combined vitrectomy and
phaco surgery to put artificial lenses in cases of cataract.
* Complication
- Complications during surgery: bleeding, retinal tear ...
- Complications after surgery: Hemorrhagic hemorrhage (early, late),
retinal detachment, glaucoma and glaucoma, cataract, infection
1.2. BEVACIZUMAB IN OCULAR TREATMENT
1.2.1.Structure: Bevacizumab (Avastin, Genetech Inc., San Francisco,
CA) is a monoclonal immunoglobulin, combining VEGF through 2
antigen-binding sites.
1.2.2.Pharmacokinetics: The drug exists in vitreous more than 30 days
after a dose of 1.25mg / 0.05ml.
1.2.3. Mechanism: the drug penetrate the blood-retina barrier,
combined with all types of VEGF. VEGF inhibitors cause temporary
vasoconstriction, new vessels regress completely within 48 hours and
maintain for 4 weeks. After injection, there is a decrease in both the
number and aperture of new vessels that will then develop fibrosis.
1.2.4. Indication: to treat proliferative diabetic retinopathy: reduces
new vessels of iris, optic disc, retina and reduces vascular leakage,
hemorrhage.
1.2.5. Side effects
1.2.5.1. Systemic side effects: reduced wound healing, hypertension,
myocardial infarction, stroke, even death.
1.2.5.2. Ocular side effects after injection (side effects of the drug
and injection technique): subjunctival hemorrhage, intraocular
inflammation, retinal tear ...
1.3.
THE
COMBINATION
OF
INTRAVITREAL
BEVACIZUMAB
AND
VITRECTOMY
TO
TREAT
PROLIFERATIVE DIABETIC RETINOPATHY
1.3.1.Indications
Severe vitreous hemorrhage/ fibrovascular membrane/ tractional
macular detachment/ tractional retinal detachment with retinal tear


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1.3.2.Researchs on combination therapy: Increased VEGF
concentration in vitreous of proliferative diabetic retinopathy eye is a
risk factor for failure of vitrectomy. Intravitreal injection of anti-VEGF
drugs reduces VEGF levels in the vitreous cavity of proliferative
diabetic retinopathy eye.
* Drugs: Ranibizumab and Bevacizumab are rated equally on the
effectiveness of treatment and safety. The larger molecular size of
Bevacizumab should have the advantage of treating proliferative
diabetic retinopathy.
* Dose: the effect of intravitreal injection Bevacizumab for proliferative
diabetic retinopathy is not significantly different with the dose ranging
from 1.25mg, 2.5mg to 6.2mg. Currently the common dosage is 1.25mg
/ 0.05ml.
* Time between injection and vitrectomy: In the treatment of
proliferative diabetic retinopathy, Bevacizumab is injected before or at
the end of the surgery. Preoperative Bevacizumab injection is better
because the drugs makes it easily to dissect fibrous proliferative
membrane, laser photocoagulation, limit bleeding during surgery,
postoperative complications.
* Studies using Bevacizumab (1.25mg / 0.05ml) intraocular
injection before vitrectomy: the authors in the world report that
intravitreal Bevacizumab injection (1.25mg / 0.05ml) preoperative 1-2
weeks in the treatment of proliferative diabetic retinopathy has good
anatomical results, increased postoperative vision, limiting bleeding and
tears in surgery, limiting recurrent bleeding after surgery . In Vietnam,
the author Nguyen Thi Nhat Chau reports the results of using
Bevacizumab in combination with vitrectomy for treatment of diabetic
retinopathy, but the study was conducted on a small scale with short
follow-up time, didn’t analyse related factors to the outcome.
1.3.3.Related factors to the outcome of treatment
1.3.3.1.Systemic factors:age, duration of diabetes, high blood sugar,
hypertension, diabetic kidney disease ...


9
1.3.3.2.Ocular factors related to treatment outcome
* Diagnosis: vitreous hemorrhage gain the best result after treatment,
vitreous hemorrhage accompanied by fibrosis proliferation also has
good result if there are no complications or well-treated surgical
procedures. Vitreous hemorrhage with retinal detachment have the
worst prognosis results.
*Complications: complications during surgery (bleeding, retinal
tear,..), postoperative complications ( vitreous hemorrhage, iris
neovascular, retinal detachment, cataract, infection. .)
* Additional treatment
- Additional injections: recurrent vitreous hemorrhage, neovascular
glaucoma
- Additional surgery: additional surgery affects the results of anatomy,
visual acuity and visual quality.


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CHAPTER 2
SUBJECTS AND METHODS
2.1.Subjects: The study was conducted on severe proliferative diabetic
retinopathy patients with vitreous hemorrhage complications who were
examed and treated Retinal Department of National Institute of
Ophthalmology, from January 1, 2012 to December 30, 2016.
2.1.1.Selection criteria
- Patients aged 18 years or older
- Diagnosed with proliferative diabetic retinopathy with vitreous
hemorrhage:
+ Vitreous hemorrhage does not clarify the fundus (grade II, III)
+ Vitreous hemorrhage with fibrosis proliferation or vitreous
hemorrhage with retinal detachment of macula.
-Agree to join the research
2.1.2.Exclusion criteria
- Patient has a history of vitrectomy
- Patients currently have other eye diseases such as trauma, progressive
inflammation, new glaucoma, etc.
- Patients with severe systemic diseases such as systemic disease,
tuberculosis ...
- If after intravitreal Bevacizumab injection, hemorrhage is fully
absorbed or there is small amount of hemorrhage (grade I) without
fibrosis proliferation/ retinal detachment patients move to do laser.
2.2.Methods
2.2.1.Study design: Intervention study had no control group.
2.2.2.Sample size : n=68

2.2.3.Sampling method
All patients eligible for study were selected up to the sufficient number
2.2.4.Research tools
2.2.4.1.Examination tools
2.2.4.2.Surgical tools: Surgical instruments and machines
2.2.5.Realization steps
2.2.5.1.Medical history records


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2.2.5.2. Clinical examination
* Vision function: best corrected visual acuity with Snellen eye chart
* Evaluation the intraocular pressure
* Examining and evaluating the ocular surface condition, anterior
chamber,iris, pupil, crystal lens
* Examining and evaluating vitreous and retina
2.2.5.3.Tests: blood tests of blood,ultrasound, fluorescence
angiography, OCT..
2.2.5.4. Diagnosis of proliferative diabetic retinopathy with vitreous
hemorrhagecomplications:
Vitreous
hemorrhage/
fibrosis
proliferation/ tractional retinal detachment/tractional retinal detachment
with retinal tear .
2.2.5.5.Intravitreal Bevacizumab injection
* Preparing the patient: applying mydriasis medication, antiseptic
skin, anesthetic
* Dosage and method of injection: Using speculum, using a needle
27-30 G, injecting 0.05ml of Bevacizumab solution with the content of
1.25mg into the vitreous chamber through pars-plana in the temporal
region below the cornea of the cornea 3.5- 4mm, small antibiotic
moxifloxacin (Vigamox) 4 times / day after injection for 5 days.
2.2.5.6. Vitrectomy: after injection Bevacizumab vitreous chamber
from 1-2 weeks.
* Preparing patients: dilated pupils, antiseptic, anesthesia next to the
eyeball.
* Surgery: Open the eyeball through the pars plana 3.5-4mm from the
edge to create a way for infusion, lights, cutters. Vitrectomy using a 20
or 23 gauge system under a wide-angle optical system or through an
intraocular camera. Cut out the hemorrhagic from the center to the
periphery, treat the posterior vitreous membrane, dissect and cut the
fibrous membrane, stop bleeding, retinal laser, using tamponade
replacement, close the entrance. Cataract surgery if needed.
2.2.5.7. Treatment after surgery
* Anti-inflammatory treatment


12
* Treatment of complications: glaucoma, cataract, vitreous
hemorrhage, retinal detachment, pre-retinal membrane, neovascular
glaucoma, macular edema ...
2.2.6. Evaluation criteria
2.2.6.1. Evaluation the characteristics of the patient
* Systemiccharacteristics
* Ocular characteristics
2.2.6.2. Evaluate the outcome of treatment
* Evaluation after intravitreal injection: time of injection before
surgery, average vision, intraocular pressure, systemic complications,
ocular complications.
* Surgical evaluation
 Surgical indications: Vitreous hemorrhage, fibrous membrane,
retinal detachment ± tear
 Evaluation intraoperative
- Surgical techniques: segmentation, fragmentation, en-bloc, combined
technique
- Tamponade: water, air, gas (SF6, C3F8), Silicon oil.
- Cataract surgery
- Surgical complications: hemorrhage, cataract, retinal tear, retinal
detachment and other complications.
*Postoperative evaluation: 1 week, 1 month, 3 months, 6 months, 12
months, 24 months after surgery
- Assessing vision results:
+ Average vision is calculated by logMar
+ Vision group: Good, fair, poor
+ Increased vision
. Increased vision acuity after treatment: Visual acuity after the
evaluation increases at least 1 row compared to the previous evaluation.
In the case of eyesight at counting fingers, calculating counting fingers
3m with visual acuity increases compared to counting fingers 2m and
counting fingers 1m, counting fingers 2m has increased over counting
fingers 1m (when converted to logMar vision, the next evaluation has
lower value than previous value)


13
. No increased visual acuity after treatment: visual acuity stays the
same or worse than pre-treatment visual acuity. In the case of visual
acuity at counting fingers level, if the visual acuity is still between ≤ 1
meter between 2 assessments, the visual acuity will not increase.
- Evaluating postoperative surgery results
+ Success: complete clear environment of the components of the
fundus, no neovascular and fibrous membranes on the retina, optic disc,
retinal attachment, retinal neovascularization does not progress further.
+ Failure: opaque vitreous obscures the central retina or the entire
retina, the fundus is not illuminated or retinal detachment, there are
persistent retinal fluid shrinkage, neovascular continue to evolve, and
neovascular glaucoma.
-Complications after surgery: recurrent vitreous hemorrhage, uveitis,
endophthalmitis, cataract, retinal detachment, ocular atrophy, and other
complications.
* Additional treatment: additional injections, additional surgery.
* General evaluation
* Successful surgery
- Anatomical results: remove blood in the vitreous chamber, remove
all the hyaloids later, remove the fibrous proliferating membrane and
contract.
- Vision increased at the time of examination compared with vision
before treatment
* Surgery failure: when either of the 2 criteria or both criteria on
vision and surgery are missing.
2.2.6.3. Evaluate factors related to treatment results
* Systemic factors associated with the outcome of treatment
* Ocular factors associated with the outcome of treatment:
diagnosis, complications, additional treatment.
2.2.7. Data processing: SPSS 18.0 statistical software. Tested by Tstudent algorithm and when squared, test Phi.
2.2.8. Research ethics


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CHAPTER 3
RESULTS
3.1.PATIENT CHARACTERISTICS IN PRE-TREATMENT
A total of 68 eyes that were studied, considering each eye to be an
individual with independent systemic characteristics.
3.1.1. Systemic characteristics: The mean age was 57.3 ± 8.4 years, in
which aged under 64 years accounted for 82.4%. The percentage of
males and females was 58.8% and 41.2%, respectively. Mostly type 2
diabetes was identified in this study. The mean duration of diabetes was
12,2 ± 6,8 years, in which the duration that under 15 and over 15 years
were 60.3% and 39.7%, respectively. Unstable treatment of diabetes
was 97.1%, in which the rate of using Insulin was 75%. Besides, the
incidence of hypertension and diabetic nephropathy was 83.8% and
29.4%, respectively.
3.1.2. Ocular characteristics
3.1.2.1. Related characteristics: The mean duration of diabetic
retinopathy was 9,4 ± 11,7 months. Patients treated with laser therapy
before being included in this study was 16.2% and no laser therapy was
83.8%.
3.1.2.2. Clinical findings:
* Visual acuity: The mean visual acuity was 1.52±0.34 (logMar)
(Counting finger 2 meters). Poor visual acuity (≤ 20/400) accounted for
85.3%, while visual acuity ranged from 20/200 to 20/80 was 14.7%, no
good visual acuity (≥ 20/63) in this study.
* Intraocular pressure:Normal .
*Diagnosis characteristics: 100% eyes with vitreous hemorrhage,
of these, 77.9% were vitreous hemorrhage and 22,1% acootractional
retinal detachment. Grade I, II, III vitreous hemorrhage was accounted
for 13.2%, 35.3%, 51.5%, respectively, showed significantly statistical
difference.
* Posterior vitreous detachment characteristics: Complete,
incomplete and no posterior vitreous detachment was 4.4%, 48.5%,
47.1%, respectively. Posterior vitreous detachment in eyes with vitreous
hemorrhage (45.3%) was significantly statistical difference, compared


15
with eyes with vitreous hemorrhage and tractional retinal detachment
(80%).
* Fibrovascular membrane characteristics: Fibrovascular
membrane was reported 47.1%, no fibrovascular membrane was
reported in 52.9% of cases.
* Lens characteristics: Cataract was found in 91.2%, no cataract
was 4.4%, intraocular ocular lenses was 4,4% of cases, respectively
3.2. TREATMENT OUTCOME
3.2.1. Evaluation after intravitreal injection
* Preoperative injection timing: range 5-14 days, in which 20 eyes
had preoperative injection accounted for 29.4% (range, 10-14 days)
* Mean of visual acuity: After intraocular injection, mean of visual
acuity was 1.5 ± 0.39 ( logMar) ( approximately counting finger
2meters)
* Intraocular pressure: 100% normal
*Complications: There were 66 eyes (97.1%) without complications
and 2 cases (2.9%) with subconjunctival hemorrhage.
3.2.2. Surgical evaluation
3.2.2.1. Surgical indication
- There were 53 eyes (77.9%) with grade I,II,III vitreous
hemorrhage, in which 18 cases with fibrovascular proliferation. There
were 3 eyes diagnosed Grade I vitreous hemorrhage with fibrovascular
proliferation. 19 eyes diagnosed Grade I vitreous hemorrhage of which
5 eyes with fibrovascular proliferation. 31 eyes with Grade III vitreous
hemorrhage of which 5 eyes with fibrovascular proliferation
- In case of vitreous hemorrhage with tractional retinal detachment,
we documented 15 eyes (22.1%) in our study.
3.2.2.2. Intraoperative evaluation
* Surgical technique: 91.2% En-bloc technique, 8.8% combined
technique
* Intraocular tamponade: Using fluid, air, gas and silicon oil
accounted for 61.7%, 16.2%,16.2%, and 5.9%, respectively.
* Cataract surgery:Combined cataract surgery with vitrectomy was
reported in 58 eyes (85.3%).


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* Intraoperative complications: No complications (58.8%),
hemorrhage without retinal tear (23.5%), retinal tear ( 17.7%).
3.2.2.3. Post-operative evaluation
* Visual acuity
- The mean visual acuity at 1-week, 1-month, 3-month, 6-month
postoperative follow-up was 1.26 ± 0.42, 0.98 ± 0.52, 0.78 ± 0.51, 0.75
± 0.53 LogMar, respectively. At 12-month postoperative follow-up in 67
eyes, the mean visual acuity was 0.74± 0.53.At 24-month postoperative
follow-up in 66 eyes, the mean visual acuity was 0.78± 0.53. The visual
acuity at 3, 6, 12, 24 months postoperatively was no significantly
different (p>0.05).
- The visual acuity was divided into 3 groups, in which the initial poor
vision in this study was 85.3% (58 eyes). Visual acuity was not improved
after having Bevacizumab intravitreal injection. 1-week postoperative ,
the good visual acuity was documented in 4 eyes (5.9%), while most of
patients had poor visual acuity 42 eyes (61.8%). At 1-month, 3-month, 6month postoperative the visual acuity was improved in 13 eyes (19.1%),
31 eyes (45.6%), 34 eyes (50%), respectively. At 12 months and 1 year
follow-up, good visual acuity was determined in 30/67 eyes (44.8%) and
31/66 eyes (47%), respectively. In group of moderate vision acuity, there
was an improvement identified at preoperative, postoperative and a longterm follow-up. In visually impaired group, there was markedly
decreased from postoperative to the time of 3 months follow-up (poor
visual acuity was documented in ¼ patients).
- The incidence of improved visual acuity after surgery 1-week
(57.4%), 1-month (72.1%), 3-month (85.2%), 6-month (80.9%), 12month (80.6%) , 24-month (80,3%). In a group of moderate and good
visual acuity, the incidence of increased visual acuity postoperatively
that compared with pretreatment was significantly different (p <0.001)
* Anatomical outcome: The successful anatomical outcome after 24
months follow-up was 80.3%. There was no significant difference
between preoperative and postoperative timing.
* Postoperative complications: 1 eye could have several
complications


17
- Vitreous hemorrhage: Of which 26 eyes (38.2 %), there were 4
eyes (5.9%) with early hemorrhage postoperative follow-up, 4 eyes
( 5.9%) with early hemorrhage as well as postoperatively progressive
hemorrhage. Besides, there were 18 eyes with late hemorrhage
accounted for 26.5% of cases.
- Retinal detachment was noted in 3 eyes (4.4%)
- Neovascular glaucoma was noted in 3 eyes (4.4%)
- Other complications were reported including epiretinal membrane
in 4 eyes (6%), choroidal detachment in 1 eye (1.5%), cataract in 2 eyes
(3%), glaucoma in 1 eye (1.5%).
- Macular edema was reported in 44 eyes (64.7%), in which focal,
diffuse tractional edema was accounted for 8.8%, 47.1%, 8.8%,
respectively.
3.2.2.4. Additional treatment
* Additional postoperative intravitreal injection of Bevacizumab
1.25mg/ 0.05ml: 32 of 44 eyes with macular edema (72.7%), 10 eyes
(22,7%) presented recurrent vitreous hemorrhage and neovascular
glaucoma (4.6%).
* Additional surgery: The require for surgery at the first, second,
third and four times was noted in 50 eyes (73.6%), 10 eyes (14.7%), 6
eyes (8.8%), and 2 eyes (2,9%), respectively. There were totally 96
times that required surgical intervention.
3.2.2.5. Surgical outcomes: The result of 24-month postoperative
follow-up was 74.2%.
3.3. SOME FACTORS RELATED TO TREATMENT OUTCOME
At 24-month postoperative visits, we documented 66 eyes. Many
factors are affected to treatment outcomes. However, to evaluate the
final results, we concern about visual and anatomical outcomes.
3.3.1. Systemic factors related to treatment outcome
* Systemic factors related to visual improvement:
No correlation between visual acuity that detected at 24-month
postoperative follow-up compared with pretreatment: gender, age
group, duration of diabetes, improvement in Glycemic Control, use of
insulin, hypertension, kidney disease.


18
* Systemic factors related to anatomical outcomes: No correlation
between postoperative anatomical outcomes: gender, age group,
duration of diabetes, improvement in Glycemic Control, use of insulin,
hypertension, kidney disease.
3.3.2. Ocular factors related to treatment outcome
3.3.2.1. Diagnosis
*Correlation between diagnosis and postoperative improved
visual acuity: Compared to pretreatment outcomes, improved visual
acuity in vitreous hemorrhage group (82.4%) showed no difference in
comparison to vitreous hemorrhage with retinal detachment group
(73.3%) (p> 0.05)
* Correlation between diagnosis and visual acuity group
The visual acuity of vitreous hemorrhage group and vitreous
hemorrhage with retinal detachment group at preoperative, postinjection evaluation was mostly poor vision group. After surgery, good
visual outcome in vitreous hemorrhage group was higher than vitreous
hemorrhage with retinal detachment group (p< 0.05).
*Correlation between diagnosis and anatomical outcome: The
successful anatomical outcome of vitreous hemorrhage group (80.4%)
showed no difference compared with vitreous hemorrhage with retinal
detachment group (80%) (p>0.05)
3.3.2.2. Complications
* Intraoperative complications:
- Fibrovascular membrane is a factor affected to intraoperative
complications.
- The rate of improved visual acuity, good, moderate, poor visual
acuity and poor anatomical outcome in a group of no complications
showed no significantly statistical difference, comparing with a group
of complications (p > 0.05)
* Postoperative complications:
- Correlation between postoperative complications and improved
vision: The rate of improved vision in a group of no complications
(93.9%) showed no significantly statistical difference, comparing with a
group of complications (66.7%) (p > 0.05)


19
- Correlation between postoperative complications and visual
acuity group: The rate of good visual acuity in a group of no
postoperative complication (66.7%) presented significantly statistical
difference, comparing with a group of complications (27.3%) (p>0.05)
- Correlation between postoperative complication and
anatomical outcome: A group of no postoperative complication
presented with 100% successful anatomic outcomes. In a group of
complication, anatomic outcome was achieved successfully in 60.6%
cases and failed in 39.4% cases.
- Correlation between postoperative macular edema and
improved visual acuity: The rate of postoperative group without
macular edema (72.7%) presented no statistical difference, comparing
with a group of macular edema (84.1%)
3.3.2.3. Additional treatment
*Additional intravitreal injection: As the improved visual acuity at
24-month follow-up compared with pretreatment, visual acuity and
anatomical outcome showed no significantly statistical difference
between two groups of additional injection and non-additional injection.
* Additional surgery
- Correlation between additional surgery and improved visual
acuity: As the improved visual acuity at 24-month follow-up compared
with pretreatment, there was significantly statistical difference between
two groups of additional surgery (44.4%) and no additional surgery
(93.8%)
- Correlation between additional surgery and visual acuity: The
result of visual acuity in a group of no additional surgery (62.5%) was
significantly statistical difference, comparing with a group of additional
surgery (5.6%).
- Correlation between additional surgery and anatomical
outcome: The rate of successful anatomy in a group of no additional
surgery (89.6%) was significantly statistical difference, comparing with
a group of additional surgery (55.6%)


20
CHAPTER 4.
DISCUSSION
4.1. PATIENT CHARACTERISTICS BEFORE TREATMENT
4.1.1. General characteristics: The mean age was 57.3 ± 8.4, under 64
years old accounted for 82.4%. There was no significant difference in
sex ratios, corresponding to the results of Bandello, El-Batany… Our
study is mainly on type 2 diabetes patients. The mean duration of
diabetes was 12.2 ± 6.8 years, in which the duration was under 15 years
accounted for 60.3%, the rate of using Insulin was 75%, ineffective
glycemic control was 97.1%, hypertension rate was 83.8%, kidney
disease was 29/4%, resulting in Diabetic Retinopathy.
4.1.2. Ocular characteristics
4.1.2. Ocular manifestations
4.1.2.1. Related characteristics: The mean time of diabetic retinopathy
course was 9.4 ± 11.7 months, including 16.2% eyes with preoperative
incomplete laser treatment and 83.8% eyes with no treatment. The
longer time of diabetic retinopathy course, the higher chance of getting
worse, particularly, if diabetes is left untreated or improperly treated.
4.1.2.2. Clinical ocular manifestations: The mean of postoperative
visual acuity was 1.52±0.34 (logMar), primarly poor vision. In our
study, the percentage of normal IOP was 100%, 77.9% eyes with
vitreous hemorrhage, 22.1% eyes with vitreous hemorrhage and
tractional retinal detachment. Vitreous hemorrhage, proliferative fibrotic
membranes or tractional retinal detachment are causes leading to visual
impairment.
- The percentage of incomplete posterior vitreous detachment and no
posterior vitreous detachment was 48.5%, and 47.1%, respectively. The
progression of proliferation related to posterior vitreous detachment
leading to an increased force in the adhesion area of the vitreous to the
retina causes several complications, such as vitreous hemorrhage, and
tractional retinal detachment. The percentage of posterior vitreous
detachment in vitreous hemorrhage group was 45.3%. The difference


21
was statistically significant, compared to vitreous hemorrhage and
tractional retinal detachment group accounted for 80% of cases.
- Fibrovascular membrane was found in 47.1% of cases.
Neovasculazation and fibrous tissue primarly develop along the surface
of posterior hyaloid membrane. With regards to posterior vitreous
detachment, fibrovascular membranes further develop in vitreous
cavity, leading to an increase of tractional force at the vitreoretinal
adhesion, causing complications such as vitreous hemorrhage and
retinal detachment.
- Older participants in this study were diagnosed with diabetic
retinopathy, therefore, most of research eyes were diagnosed with
cataracts (91.2%)
4.2. TREATMENT RESULTS
4.2.1. Evaluation after intravitreal injection
- Preoperative intravitreal injection of Bevacizumab was accounted
from 5 to 14 days. The proportion of eyes required surgical therapy after
having intravitreal injection from 10 to 14 days due to the high blood
surgar level was 29.4%.
- The mean visual acuity after intravitreal injection was 1.5 ± 0.39
logMar. After having intravitreal injection, treated eyes still suffered
dense vitreous hemorrhage. In case of eyes with mild vitreous
hemorrhage, we documented there was a proliferative fibrovascular
membrane as well as tractional retinal detachment causing visual
impairment.
- Intraocular pressure after injection was completely normal for all
eyes. This study only injected slowly 0.05 ml so that there was no
elevated IOP in follow-up visits.
- Complications: no systemic complications because the participants
with myocardial infarction or history of stroke were excluded in this
study. The incidence of patients in whom subconjunctival hemorrhage
was 2.94%.
4.2.2. Surgical evaluation


22
4.2.2.1. Surgical indication: After Bevacizumab intravitreal injection,
there were 3 eyes with grade I vitreous hemorrhage and proliferative
fibrovascular, 19 eyes with grade II vitreous hemorrhage, 31 eyes with
grade III vitreous hemorrhage, 15 eyes with vitreous hemorrhage and
retinal detachment that required surgical intervention. The indication of
vitrectomy is to eliminate hemorrhage as well as traction to make retina
reattach.
4.2.2.2. Intraoperative evaluation:
* Surgical technique: 62 eyes (91.2%) required En-bloc technique,
6 eyes (8.8%) needed combined technique. The complexity of
vitrectomy for diabetic retinopathy depends greatly on the condition of
the adhesive vitreoretina.
* Intraocular tamponade: The selection of intraocular tamponade
based on preoperative lesions and intraoperative complications. Silicon
oil was used in 5.9% of cases due to complications, such as retinal tear,
retinal tear combined with intraoperatively intensive hemorrhage that
prevent performing laser therapy.
* Cataract surgery: The percentage of eyes combined with cataract
surgery
was
85.3%.
Regarding
vitrectomy
combined
phacoemulsification and IOL implantation, the view of operative field
for surgeons will be better and easier to perform clear vitrectomy,
manage fibrovascular membrane, retinal lesions and laser therapy for
peripheral retina
* Intraoperative complications:Hemorrhage was found in 23.5%
of cases, while retinal tear was identified in 17.7% of cases. Retinal tear
in this study is lower than N.N.Chau’s study (27%). The reason is that
we performed Bevacizumab intravitreal injection before surgery,
therefore, fibrovascular membrane was limited progressively as well as
the removal of this membrane was easier, being effective in the
prevention of intraocular complications.
4.2.2.3. Postoperative evaluation
* Visual acuity outcome:


23
- The mean visual acuity of postoperation was better (LogMar).
Vision is relatively stable from 3-month follow-up. At 24-month followup, the mean visual acuity was 0.78 ± 0.53.
- Visual acuity group: Visual improvement was achieved gradually.
Good vision occured 1-week postoperation, greatly improved and being
stable from 3-month follow-up. Moderate and good vision in our study
(74.3%) and Khan’s study (78%) are higher than N.N.Chau’s study
(50.9%). The reason is that our study and Khan’s study performed
Bevacizumab intravitreal injection before surgery, therefore,
intraoperative and postoperative complications are limited.
- The rate of postoperative improved vision is gradually increased.
The percentage of increased visual acuity was 80.3%, similared to
Khan’s study (78%). The visual acuity of a group of moderate-good
vision was higher than a group of no improvement.
* Anatomical outcome: The result of successfully anatomical
outcome in our study was 80.3%, being higher than NN.Chau’s study
(72.2%). The reason is that we performed Bevacizumab intravitreal
injection before surgery, making neovascular degenerated in quality as
well as aperture. Therefore, the dissection of fibrous membranes
become easier and managing lesions well, leading to fewer
intraoperative and postoperative complications.
* Postoperative complications: 26 eyes had postoperative vitreous
hemorrhage (38.2%). Bevacizumab preoperative intravitreal injection
help manage retinal lesions, reduces intraoperative complications and
limits postoperative hemorrhage. Most of postoperative hemorrhage
was mild and be diminished by medical treatment. The percentage of
retinal detachment was 4.4% and visual acuity was not improved by
vitrectomy. Neovascular glaucoma was a severe complication and not
responded with treatment. Other complications: cataract, epiretinal
membrane, high IOP, choroidal detachment, require additional surgical
intervention.


24
- Regarding macular edema, apart from the great role of tractional
factor, edema would be remarkably reduced after 2-week follow-up of
vitrectomy. Therefore, other types of edema are not presumptive as
complications or pre-existing lesions of diabetic retinopathy. However,
we reported that ocular manifestation has only been found after surgery.
4.2.2.4. Additional treatment
* Additional injection:Bevacizumab additional intravitreal injection
is indicated for macular edema, recurrent postoperative vitreous
hemorrhage, resulting in improved visual acuity. Bevacizumab’s effect
would be benefit in reducing the pathogenesis of edema and increasing
blood absorption in vitreous cavity to limit additional vitrectomy. The
injection of Bevacizumab in neovascular glaucoma is to degenerate
neovasular in retina and iris and lower IOP, preventing hemorrhage but
the results showed no positive.
* Additional surgery:A total of eyes required the secondary, third
and fourth surgery was 14.7%, 8.8% and 2.9% of cases, respectively.
There is a variety of additional surgery, such as retinal detachment,
recurrent vitreous hemorrhage, neovascular glaucoma, cataract,
epiretinal membrane, high IOP and choroidal detachment...
4.2.2.5. General evaluation of treatment outcomes: Treatment
outcome was successful in 74.2% of cases when Successful treatment
outcome was 74.2% of cases when the success of visual acuity and
anatomy were achieved at the time of evaluation.
4.3. FACTORS RELATED TO TREATMENT OUTCOMES
At 24 months follow-up, we examined 66 eyes in the study.
Although there are many factors related to treatment outcomes, we take
into account the
visual and anatomical outcomes.
4.3.1. Systemic factors related to treatment outcomes: Age, sex, and
duration of diabetes were not related to the results of treatment. No
association was identified between blood sugar level control, use of
insulin, hypertension, kidney disease and treatment outcomes due to this


25
study has been conducted to a limited data, and whole body condition of
patients was severe at the time of presentation.
4.3.2.Ocular manifestation related to treatment outcomes
4.3.2.1. Diagnosis: There is no difference of improved visual and
anatomical outcomes between a group of vitreous hemorrhage and
vitreous hemorrhage with retinal detachment. The effect of the
treatment improves the quality of vision, postoperative recovery of
visual acuity is gradually progresses to a good vision. Good vision
results in a vitreous hemorrhage group is higher than a group of vitreous
hemorrhage with retinal detachment (p<0.05). Vitreous hemorrhage
masks the optical axis but the retina has not been seriously damaged.
Apart from vitreous hemorrhage with retinal detachment, tractional
retinal detachment separates the retinal nerve layer from the retinal
pigment epithelium, in particular, detached area spreads to the fovea
causing severe visual impairment.
4.3.2.2. Complications
*Intraoperative complications: Fibrovascular membrane is a factor
contributed
to
intraoperative
complications.
Bevacizumab
preoperatively intravitreal injection makes neovasculazation
degenerated, so that resulting to reduce new hemorrhage as well as
manage well intraoperative complications. Thus, it has not been affected
to treatment outcomes.
*Postoperative complications: There is a correlation between
postoperative complications and anatomical outcomes, improved visual
acuity. Intensive management of complications still has the certain rate
of failed anatomical outcomes. The rate of improved vision, good vision
in a group of no complication is higher than a group of complication
(p<0.05). Pathogenesis of diabetic retinopathy is not complicated but
also postoperative complications added, leading to no visual
improvement even though clear vitreous, reattached retina after surgery
in many cases. Pathogenesis of macular edema in diabetic retinopathy is
also complicated. The percentage of improved vision in a group of no


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