Comparison of Peroperative Methotrexate Infusion With Postoperative Intra Silicon Oil Methotrexate Injections for Prevention of Proliferative Vitreoretinopathy Development After Vitrectomy for Rhegmatogenous Retinal Detachment Repair.
Phase: PHASE1
Conditions: Proliferative Vitreoretinopathy
Sponsor: University of Health Sciences Lahore

 
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NCT Number:   
 
 
 
 
 
 
Date: 24/02/2024 
Official Title 
Comparison of peroperative methotrexate infusion with postoperative intra silicon oil methotrexate 
injections for prevention of proliferative vitreoretinopathy development after vitrectomy for 
rhegmatogenous retinal detachment repair. 
Brief Title 
Comparing Methotrexate Usage Techniques to Prevent Proliferative Vitreoretinopaty After Retinal 
Detachment Vitrectomy. 
Topic of interest: Role of Methotrexate in the prevention of proliferative vitreoretinopathy 
development after pars plana vitrectomy for rhegmatogenous retinal detachment. 
Research gap: A comparison of different dosing regimens of methotrexate is not available. 
Research question.  
Which methotrexate dosing strategy is more effective in preventing PVR after retinal detachment 
surgery (PPV): perioperative infusion or sequential postoperative injections? 
Introduction 
Retinal detachment is one of the major causes of irreversible blindness 1. Increasing number of aging 
population, increasing myopia and increased number of cataract surgeries are resulting in increased 
incidence of retinal detachment 2 , 3. 
Surgical intervention is essential for the treatment of rhegmatogenous retinal detachment. With 
increase in expertise of surgeons and refined gadgets, pars plana vitrectomy is the most commonly 
performed surgical procedure for the treatment of rhegmatogenous retinal detachment 4. 
PVR is a major cause of retinal detachment surgery failure 5. Many approaches have been attempted 
to stop the development of PVR 6. Methotrexate infusion during pars plana vitrectomy has been 
tried. It has shown encouraging results in terms of prevention of development of PVR 7. Serial 
methotrexate intrasilicon oil injections are utilized. They also have showed promising results in terms 
of prevention of PVR 8.  
PVR develops in response to inflammatory cascade. PVR develops during initial postoperative period 
particularly 60 to 90 days after retinal detachment surgery 9. 

 
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Peroperative infusion of methotrexate provide loading dose. It is though that retinal tissues absorb 
methotrexate that prevents formation of PVR. This could be beneficial in the immediate 
postoperative period in stopping the development of PVR, but long-term prevention could not be 
provided. Half-life of intravitreal methotrexate is 3 to 5 days 10. Repeated doses of methotrexate 
should be needed to prevent the development of PVR in the first 2 to 3 months after pars plana 
vitrectomy. According to our hypothesis, repeated intrasilicon oil methotrexate injection should 
prevent PVR formation to a greater extent than per operative methotrexate infusion. 
Objective of this interventional trial is to compare the efficacy of repeated intrasilicon oil 
Methotrexate injections with per operatively Methotrexate infusion in the prevention of Proliferative 
Vitreoretinopathy 
Key words: Injection, Methotrexate, Proliferative vitreoretinopathy, Retinal detachment, Vitrectomy 
Methodology 
This interventional trial will be conducted at the Sahiwal Teaching Hospital, Sahiwal and Ali Fatima 
Teaching Hospital Lahore from March 2024 to May 2025. The study will follow the guidelines of the 
Declaration of Helsinki. The study protocol will be approved by institutional review boards of 
respective hospitals. Written informed consent will be taken from all the subjects. The first subject will 
be recruited in March 2024 and the last subject will be recruited in February 2025. Three more months 
will be required to complete the final follow-up of the last subject.  
The study will include rhegmatogenous retinal detachments patients of both sexes between 20 and 70 
years of age. 
Exclusion criteria will include the presence of proliferative vitreoretinopathy grade C, previous retinal 
detachment surgery in the same eye, penetrating ocular trauma, intraocular foreign bodies, previous 
glaucoma filtration surgery, allergy to methotrexate, and pregnant and lactating women. 
A detailed history of the patients’ presenting complaints, duration of symptoms, and risk factors for 
retinal detachment will be gathered. Comprehensive ocular examination, including visual acuity, 
intraocular pressure, and examination of the anterior and posterior segments, will be performed. The 
extent of retinal detachment, location of retinal breaks, and presence of PVR will be documented. 
Sampling method will be simple random sampling. Sample size will be calculated by using online 
software.  

 
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Using lottery methods patients will be divided into two groups with 60 subjects in each group. Group 
1 will be regarded as control group and per operative methotrexate infusion will be used by mixing 75 
mg of methotrexate into one litre of BSS solution.   Group 2 will be regarded as the study group and 
will receive 500 µg of intra-silicon oil methotrexate at the end of the surgery and then at 1st, 2nd, 3rd , 
4th and 6th post operative weeks.  
This will be a single-blind study in which the subjects will be unaware of the intervention. Blinding will 
be maintained by ensuring that subjects are unaware of the dosing regimens they are receiving.  
Standard pars plana vitrectomy will be performed by two surgeons, one surgeon at Sahiwal Teaching 
Hospital Sahiwal and other surgeon at Ali Fatima Teaching Hospital Lahore. Silicon oil will be used as 
post operative tamponade in all subjects. A combination of steroid and antibiotic eye drops will be 
administered eight times per day during the first postoperative week. The dosing will be tapered off 
during the next three weeks. Patients will be instructed to adopt the appropriate posture according to 
the location of retinal breaks. 
Follow-up will be performed every week for three months. The development of PVR, occurrence of 
retinal detachment, intraocular pressure, and visual acuity will be noted. The posterior segment will 
be examined with the help of a superfield lens and wide-field contact lens for the development of PVR 
and occurrence of retinal detachment. 
The primary outcomes will be the development of PVR and the recurrence of retinal detachment. All 
patients will be followed up until the development of one of the primary outcomes or completion of 
3 month follow, whichever occurs earlier. 
Improvement in visual acuity will be secondary outcome of the study. Final visual acuity will be 
measured at completion of 3 month follow up or meeting the primary outcome, whichever is earlier. 
All information will be collected using a specially designed proforma and entered  into SPSS version 26. 
Qualitative variables, such as sex, PVR development, recurrence of retinal detachment, and 
improvement in visual acuity, will be presented as frequencies and percentages. Quantitative variables, 
such as age and intraocular pressure, are presented as mean and standard deviation. 
In this prospective study we shall investigate the differences in the development of proliferative 
vitreoretinopathy (PVR) between two distinct groups. Additionally, we shall compare the difference in 
the occurrence of re-detachment of the retina between these groups. Furthermore, we shall compare 
the improvement in visual acuity at the final follow-up visit between the two groups. As the variables 
involved will be qualitative (frequency of eyes with development of PVR, Frequency of eyes with retinal 

 
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re-detachment, and frequency of eyes with improved visual acuity), Pearson's chi-square test will be 
used to carry out the statistical analysis. Statistical significance will set at P ≤ 0.05. 
 
 
References 
 
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