Prophylactic Treatment after Retinal Detachment Surgery

Abstract  

There has been realized a number of complications developed in patients upon the completion of retinal detachment surgery. This study is a detailed and comprehensive analysis which was conducted with the aim of ascertaining the existence of these complications and whether the prophylactic treatment after retinal detachment surgery prevents further complications such as vitreoretinopathy. The study through analysis was geared towards the establishment of the complications and their solutions through treatment. The study derived most of its findings from secondary sources. Thus, the statistical method involved in this study was the inferential statistics method which was based on the analysis of the observations and findings made from previous studies. As pertains to the study design, there was the formulation of observations and experimental studies in an evidence table. All the findings from the studies were evaluated and analyzed to be inconsistent with the hypothesis statement derived. From the analysis, there are drawn outcomes and results which could be empirically inferred. The surgical procedure for the detachment can lead to complications such as developing a worsening state of visual acuity and fatalities in some cases. This hypothesis-based review confirmed the need for the prophylactic treatment to avoid the cases of complications after retinal detachment surgery. 

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Prophylactic Treatment after Retinal Detachment Surgery Prevents Further Complications such as Vitreoretinopathy 

It is confirmed that the prophylactic treatments are designed with the aim of ensuring that infections do not reoccur after retinal detachment surgery. Taking, for instance, antibiotic prophylaxes used before the actual surgery or any dental procedure to prevent bacterial infections which might arise from the surgical procedure. There is the inclusion of medications after the treatments. Eye injury is considered one of the highest potentials in the cause of disabilities such as blindness in the victims. About 40-60% of the patients with open globe injury have the potential to develop Proliferative Vitreoretinopathy (PVR) complication (Morescalchi et al., 2013). In the process of development, growth factors, as well as cytokines, drive the responses from the cellular make up through their responses leading to the development of Proliferative Vitreoretinopathy (PVR). 

As presented from this discussion through the hypothesis, there is a need for the prophylactic treatment after the retinal detachment. However, there are many cases where the retinal detachment arises from the vitrectomy process. Vitreoretinopathy is one of the known diseases which arise after the proliferation of the ectopic cells in the peri-retinal l areas. As it stands currently, the best treatment strategy for the ailment is the vitreous surgery which has been proven not to be effective following the chances of vision loss (Sadaka & Giuliari, 2012). This is as a result of the lower chances of the retinal reattachment. Therefore, it becomes important that the retinal detachment surgery is followed by a well-designed treatment procedure which can be of importance in the preventive mechanisms. 

According to the issue of discussion, the most important aspect is the consideration of the treatment mechanisms after the retinal detachment surgery which has been proved to be essential in the prevention of the vitreoretinopathy. Thus, generally, this discussion is a study to establish the validation of the statement and the applicability in the medical field. 

Methods 

Search Strategy 

In this study, information was gathered from secondary data sources. Generally, the data was obtained from scholarly databases with the main being www.Pubmed.gov and Google Scholar. As pertains to the ease of navigation, there was the use of keywords which were seen as relevant to the topic and the hypothesis therein. The most searched words for this study included: retinal detachment, prophylactic treatment, and vitreoretinopathy. The search strategy involved the criteria for inclusion and exclusion of the source based on relevance and authenticity. As regard to the exclusion criteria, the year of publication of secondary materials was more of a concern. All the articles published before the year 2012 were excluded from this study. Again, there was the exclusion of articles which were published after 2017 as most of them are still undergoing authentication. There were more resourceful studies written in some other languages. However, based on the requirements, they were excluded based on the grounds of lingual and communications. 

As per the requirements of this study, the only valid sources for this research were academic journals. Thus, the study was geared towards the relevant sources which could be laid down as consistent with the study. Therefore, all the other sources from blogs, media, and pharmaceutical companies were excluded. Another important aspect of the study was on the identification and confirmation of the quality of the sources. There was a keen review of possible biases which were seen as leaning towards the glorification of the pharmaceutical companies. The criteria for the elimination based on the quality of the source were marked by the incidences of non-professional contents and the existence of irrelevant contents such as adverts and links to other websites. It is of significance to put into consideration that in the assessment of the paper quality, there was the use of primary sources. 

Strategy for Synthesizing the Data 

In order to appropriately review the sources identified for the data synthesis, there was the formulation of an evidence table as shown in table 1 within the appendix section. In terms of the date of publications, the sources were derived from the year 2012 to 2017. In terms of the study designs, there were three main types put into consideration. The considered study types were cohorts, prospective population, and the pre-clinical engagements. For the first author reviewed, there were three levels of evidence noted. Going by the rows of evidence table, there is the place for study population in which Proliferative vitreoretinopathy with retinal detachment. The drive to the use of this source in the first row was informed by the findings that the use of C3F8 has shown a greater result of success. The second row of the evidence table was informed by the fact that there is the literature existing which can validate the therapeutic treatments in the patients with proliferative retinal vitreoretinopathy. 

The analyses were made easier because there was the literature on the preretinal membrane from the patients who are suffering from proliferative vitreoretinopathy (PVR) and Epiretinal membranes (ERMs). From the evidence table, it can be inferred that the information related to the two variables looked at in the hypothesis. The summary mainly focused on the three main sections which are seen as the most essential in the analysis. The evidence table was constructed in consideration of the most essential information which could strengthen the findings in the hypothesis. Important is that the information derived from the literature was sorted based on the year of publication as well as the level of evidence. It is important to put into account that there was some literature which scored zero in terms of the level of evidence. However, the score, in this case, was superseded by the relevance of the findings and the quality of discussion entailed. 

Results 

There was primary research aimed at finding the role played by bevacizumab injected in the silicone oil at the end of the retinal reattachment surgery for the rhegmatogenous retinal detachment (RRD) associated with severe proliferative vitreoretinopathy (PVR). It was realized that no patient developed the re-detachment within the first month. It could be established that retinal re-detachment occurred in 47.3% in the case and 36.8% for the controlled groups (Falavarjani, Hashemi, Modarres, & Khani, 2014). It should be realized that in the case group, the post-operative detachment was emphatically associated with the extensive subretinal fibrous proliferation. Additionally, there was the association of the same to pre-retinal membranes in the five-year period. Nonetheless, it was learned that sub-retinal fibrous proliferations were visible and seen only in one eye among the controlled group. This comprised 14.3% of the entire controlled group in the study. 

There was the establishment of the overall results from these two groups in which the mean interval between the retinal re-detachment and vitrectomy was recorded at 6.5 weeks with variability of 1.7 for the case group. There was a slight difference for the control group where the records stood at 6.5 weeks with a variation of 1.0 (Falavarjani et al., 2014). Looking at the two it could be ascertained that the difference is slightly higher for the case group. Thus, there is a need for treatment to prevent complications. Another study was conducted by Tavares, Nóbrega, De Novelli, and De Oliveira (2015) with the aim of evaluating the functional and anatomical outcomes upon the extraction of silicone oil for the patients with retinal detachment as well as proliferative vitreoretinopathy at a retinal care facility. There was a selected group of patients who underwent the process of follow up. It took a period of 1262 days to examine the 53 patients selected. Out of these, 14 eyes representing 26.4% underwent the cataract surgery as well as silicon oil extraction (Tavares et al., 2015). 90.5% of the eyes had in their last follow up an attached retina. After the silicone extraction, it was established that most of the patients recorded good visual and anatomical outcomes. 

In line with the overall study, there was a research conducted by Telander et al. (2016) to find out the level of the epithelial membrane protein in among the surgical patients who suffered from proliferative vitreoretinopathy as well as epiretinal membranes. As it could be drawn from the results, all the studied ERMs and PVR were giving the same medical results in the EMP2 expressions. However, the inflammatory proliferative vitreoretinopathy was realized to have a higher EMP2 than ERMs (Telander et al., 2016). From the conclusion arrived after the study, it could be affirmed that all the studied PVR and ERMs presented the EMP2 (Telander et al., 2016). The level of EMP2 was seen to be higher in all the PVR subgroups as compared to ERMs. The effect was more pronounced in traumatic and inflammatory PVR. The detection of all the EMP2 was enabled by the use of RT-PCR to all the samples put in the study. It was established upon the review of this article that EMP2 and ERMs could indicate the difference in the patients with PVR. Thus, as seen from the conclusion, information extracted could be of importance in the evaluation and treatment of PVR diseases. There was a summary of data based on their preciseness and quality of information therein. 

There was another study by Sadaka et al. (2016) whose objective was an evaluation of the intravitreal methotrexate infusion (IMI) during the process of the pars plana vitrectomy (PPV). This study was exclusive to the retinal detachment especially for the patients with potential risks for the development of proliferative vitreoretinopathy (PVR). The method of data extraction was on the patients with a history of severe ocular inflammation who underwent the IMI treatments. It is ascertained that the eyes fall into a risk of proliferative vitreoretinopathy development when there is a history of prior proliferative vitreoretinopathy. 

During the pars plana vitrectomy (PPV) there was 28 patients whose total eyes placed for the study were 29 in total. Out of these, there were 17 male right eyes. The mean age for the patients was 56 years. It was ascertained that prior to the surgery with IMI all the eyes had a median of two PPVs. Significantly; the PPV conducted was 25 gauge in 76% of the total eyes; 17% had 23 gauge and 20 gauge for the 7%. Out of the 7% selected for the 20 gauge, there was the application of ocular endoscopy (Sadaka et al., 2016). A total of 90% of the eyes underwent the membrane peeling of the PVR. Further to that, there was the performance of endolaser in all the eyes included. The mean period follow-up for the study was 27 months. 

There were reattachments of retinas at the conclusion of all the surgery processes. Within the 6 months in which a postoperative was conducted, it was found out that 90% of the retinas remained attached. However, there were three eyes which developed RD from the PVR (Sadaka et al., 2016). Out of these three eyes which developed RD two were confirmed to have a history of the open globe injury. For the remaining one, it was realized that the eye was from a patient with aniridic conditions. From the 6 months follow up, there were additional follow up which was the last for the study. 

It was found out in the last follow up that there were a total of three eyes which developed recurrent PVR but without the recurrent RD. thus, there was confirmed no requirement for further intervention. Among the patients included in this specific study, three had a history of postoperative PVR as well as the recurrent RD after they underwent PPV surgery without the use of intravitreal methotrexate infusion (IMI) (Sadaka et al., 2016). In all these three patients, contralateral eyes were found to have the same initial pathology like the ones which received IMI. One of the eyes had pars planitis and developed PVR; another eye had an RD the last among the three eyes had a macular hole. 

It was observed that the culture medium which contains 12% of FBS fibroblast growth factor (FGF), insulin-like growth factor, ascorbic acid, heparin, epithelial growth factor (EGF) induced a survival as well as the growth of C-PVR cultures. An inspection done after four weeks revealed that the human cells from PVR-3 and PVR-5 had a rapid growth and displayed unique morphologic features as well as growth behavior within the cultures ( Amarnani et al., 2017) . From the results, it was evident that after 1 week of culture process the PVR-3 formed a monolayer. After the 4 weeks of culture in PVR medium, there was the formation of bands at the cells, particularly in PVR medium. On the same note, C-PVR from the clinical studies PVR-5 grew for over 1 week thus forming a confluent monolayer. 

Nevertheless, in the fourth week, PVR-5 cells appeared to grow above one another. Important for the results is that all the CPVR cultures were observed to be forming the membranes and some structures band like shaped in the culture of the human conditions. Another experiment was on the assessment of the effects of MTX on the C-PVR cells. There was an examination of the responses exhibited by C-PVR cells on the MTX. From the observation, it was evident that MTX had a significant effect of reducing CPVR bond formation, proliferation and number of cells. When the two drugs which are used in the treatment of PVR were applied daunorubicin and dexamethasone, there was no significant reduction in proliferation ( Amarnani et al., 2017) . Nonetheless, it was found out in another experiment that MTX treatment involving different concentrations has no impact on the migration imposed by the standard culture conditions of the human body. In finding out whether the death of cells contributes to the effects of MTX on the C-PVR, it is observed that increasing the concentration of MTX enhances the death of cells over time. 

There was no detection of any difference in axonal retraction with the treatment using Fasudil in the detached area as compared to the untreated detached area. Also, there was no difference between the attached and detached areas of all the retinal eyes. Hence it could be inferred that 1mM of Fasudil had no impact on the retraction. However, significantly retraction occurred faster approximately 2 hours after the process of detachment. The retraction was also present at the area where detachment occurred together with areas distance away from the injury site. Upon the increment of Fasudil concentration, there was a reduction of axon retraction (Townes-Anderson et al., 2017). There was also a decrease in the ONL length in number of SV2 labeled. It was generally deduced that injection of a higher concentration of Fasudil in subretinal injection basically reduced axon retraction, particularly in the detached retina in areas where the reduction was highly pronounced. 

Fasudil was also included in the intravitreal injection so as to test for the reduction of axonal retraction after confirmation of retinal detachment. The effects of intravitreal injection with fasudil on the axonal retraction were observed. The SV2 with spots label at the ONL indicated axonal retraction. In a general overview, there was a significant axonal retraction which indicated a reduction of 28.7% among the fasudil-treated eyes as compared to BSS. There was another effect of fasudil on the reduction of phosphorylation of MLC and cofilin on the retinal explants. The ratio of cofilin to p cofilin in total was reduced upon the inclusion of fasudil treatment by 25.8 to 26.8% (Townes-Anderson et al., 2017). Again, the ratio of pMLC to MLC was reduced 23.2 to 31.4% with the inclusion of fasudil. Fasudil was also found to be effective in reducing the number of pyknotic nuclei with a statistical recording of approximately 55.7%. It could be concluded that fasudil was capable of reducing rod cell degeneration. 

Ganekal and Dorairaj (2014) conducted a study with an aim of evaluation of the efficacy of combination 5-fluorouracil and the low molecular weight heparin in the conduction of vitrectomy. These combinations are effective in the prevention of the proliferative vitreoretinopathy (PVR). There was the grouping of consecutive patients through randomized means. The study groups were having 20 people each in which study group one had patients who underwent vitrectomy through the use of intraoperative 5-FU. Among the second group, the operation was conducted without the application of adjuvants. Then there was the evaluation of patients in intervals of 1, 2, 3 and 6 months. By the end of the sixth month, 62.5% of the patients examined had reattached retina. However, there was no recorded reattachment difference among the three groups. The rate of the proliferative vitreoretinopathy (PVR) for the controlled group was standing at 55%. There was 45% of reattachment for the study group as could be established from chi-square test results (Ganekal & Dorairaj, 2014). Important is that there was no recorded significance statistically to prove the difference between these two groups categorized. 

In order to create an exclusion of the unknown nonspecific targets found in shRNAs for the PIP4K2A/2B in humans, there was the expression of PIP4K2A/2B mouse in the ARPE-19 cells. The expressed PIP4K2A/2B mouse had their endogenous PI5P4K α and –β Knocked down by the shRNAs. Significantly, the idea of expressing mouse PI5P4Kα and –β created a restoration of the capabilities in the RV-enhanced concentration. It could be concluded from the experiment that the RV-induced expression in the PI5P4Kα and -β coordinates with the loss of p53 to bring the enhancement of cell contraction and PI5P4Kα and -β coordinates. Thus, PI5P4Kα and -β coordinates are the targeted therapeutic treatment for PVR. 

The examination of the effect of PI5P4Kα and -β coordinates on PVR was done by injecting the rabbit eye ARPE-19 cells whereby PI5P4Kα and -β coordinates were subjected to suppression by shRNA. Inasmuch as there were seen some fibrosis in 50 % of the rabbits, there were no rabbits injected with ARPE-19 with shPI5P4Kα and -β coordinates demonstrated progress to retinal detachment (Ma et al., 2016). Nevertheless, there was retinal detachment in 40% of the rabbits injected with ARPE-19 with the inclusion of shGFP control cells. Upon further analysis of histologic, there was an indication of fibrotic growth from the retina in stage 4PVR which were induced by shGFP ARPE-19 rabbits. However, no rabbit injected with shPI5P4Kα and -β ARPE-19 cells showed the same pathologic characteristics. 

From the observation, there were demonstrations that RCFs induces PVR in rabbits that form severely and rapidly as compared with the ones induced by ARPE-19cells. Further suppression of shPI5P4Kα and -β ARPE-19 reduced the RCF contractibility which was induced by the RV. The process of the demonstration was conducted in stages and periods. In all the stages the retinas get detached. However, there were no rabbits which had developed any stage of PVR by day 7. On day 28, all the rabbits whose retinas had been injected with shGFP RCFs had detachments on their retinas. 60% of the rabbits which were injected with sh PIP4K2A/B RCFs all remained at the 0 stage. 40% of the rabbits had progressed to the third stage. 

The last study was also aimed at the evaluation of the functional and anatomic results among the patients who have suffered from proliferative vitreoretinopathy (PVR) in which the treatment was retinectomy and perfluoro-octane gas (C3F8). It could be established from the findings that the primary rate of success among the patients stood at 75% (Papastavrou, Chatziralli, & McHugh, 2017). However, there was a need for examination of the remaining 25% who developed complications after the procedure. It was realized that BCVA was improved in 25% of the patients. Concerning postoperative BCVA, there were no significant differences noted in comparison with preoperative BCVA. As a matter of statistics, 25% of the patients had an improved vision while there was stability in 25% of the patients. There was deterioration in 33.3% of the patients while there were 16.7% who were lost as a result of follow-ups. 

The consequences of the PVR are marked by the growth factors especially on the vitreous. This in return stimulates the cells behind and within the retina. This occurrence is enhanced by the unavoidable impact caused by the compromised retina. There are three growth factors considered to be of importance in the enhancement of the PVR pathogenesis. Their impact is seen mainly because of the actions they remit on the PDGF receptors. These receptors are an important requirement for experimental PVR and are mostly associated with retinal diseases in human beings. There is the discovery from the study that ranibizumab reduces the rate of bioactivity of vitreous from the experimental animals and the patients who have been diagnosed by the same. Therefore, it can be conclusively stated that therapies informed by the VEGF are effective for the management of the angiogenesis which might arise upon the conclusion of prophylactic treatment after retinal detachment surgery (Amarnani et al., 2017). 

PVR is one of the complications in the retinal detachment. The primary cultures known as C-PVR reproduce and grow rapidly some of the key features of the human PVR. It is realized that one of the renowned drugs in the United States MTX can create a significant inhibition and eventual death of the C-PVR cells. Some of the drugs used in the treatment procedure such as dexamethasone and daunorubicin are not effective in the prevention of C-PVR proliferation. Therefore, the identified C-PVR can be used in testing the efficacy of therapies. Important is that the C-PVR is endowed with potentiality of identifying through screening for the new compounds which are capable of inhibiting the PVR. This has been brought out by the fact that there are not established or progress made in the development of effective treatment. Most researchers have proposed mechanisms informed by pathological factors. However, these have not been effective. Thus, it is necessary that there is the inclusion of MTX in the treatment so as to reduce the C-PVR proliferation. 

The identified agent is important in the blocking of the cellular events which causes the proliferative vitreoretinopathy. It becomes necessary in the treatment of proliferative vitreoretinopathy that the physicians are in command of the understanding of the molecular events because they are instrumental in the development of treatment design and strategies which can act as a case for reference. The injection of fasudil reduces the rod cell death after the incidences of retinal detachment, especially in the delayed treatments. Also, fasudil substance is capable of reducing the phosphorylation of MLC and cofilin within the retinal explants. According to findings from the experiment, in a normal functioning retina, there exists virtually no synaptic membrane made of protein which is immune labeled at the ONL. But approximately 2 hours after the detachment the axon retraction and synaptic protein label appeared at the ONL (Townes-Anderson et al., 2017). Fasudil injection is seen to be effective in the short-term reduction of the axon retraction as well as rod cell death. From these experiments, it is clear that there are possible applications of fasudil in the retinal recovery process. Important is that fasudil can be used in the iatrogenic retinal detachments, most of these detachments are created purposefully for the sub-retinal delivery of viral vectors, stem cells, and visual prostheses. Again, Intravitreal fasudil is seen as having potential use in the retinal degenerations which is vital for the reduction of cell death. 

Discussion 

It can be appropriately inferred that proliferative vitreoretinopathy (PVR) is one of the most common causes of the failure in the retinal detachment surgery. As per its features, the defect is characterized by a number of symptoms including migration as well as the proliferation of cells added to the fact that there are traces of inflammation. As it stands, there are a number of measures put into place to help in the curbing of these challenges. However, there is a negligible achievement of success in these endeavors. Some of these involvements include the use of drugs such as low molecular weight heparin and anti-proliferative agents. Even though there is no establishment of the role played by the VEGF in the treatment of proliferative vitreoretinopathy, there is an important and closer association between the two. The study summarizes that proliferative vitreoretinopathy is associated with the increase in subretinal and vitreous level in the vascular growth factor (Falavarjani et al., 2014). Upon the injection of Intrasilicone specifically of bevacizumab at the final stage of vitreoretinal surgery for the patients who have suffered from proliferative vitreoretinopathy, there is no prevention of PVR developments. Instead, these injections may be linked to the subretinal membrane proliferation. Considering the Prophylactic treatment after retinal detachment surgery there are reduced chances from this surgery that there can inhibitors to the development of PVR. However, there is a reduction of specific complications such as retinal membrane proliferation. 

From the scientific sources, some authors do not consider the timing given to silicone oil removal as one of the risk factors in the atomic success rates. However, as noted by some authors of the scientific and qualitative articles, shorter tamponade time periods have lower rates of attachments than longer tamponade (Tavares et al., 2015). As a result of improved surgical activities and management, there can be achieved low rate and chances of redetachment after surgical processes. Inasmuch as there are no functional outcomes which are collated with the anatomical outcomes, a longer time subjection of silicone oil with retina is likely to cause toxicity (Tavares et al., 2015). Apart from the application of surgical approaches in the treatment of PVR, there are other approaches that involve the use of drugs. Some of the commonly used and applied drugs for the treatment include daunorubicin, colchicine, and heparin. Apparently, the low rate of detachment may be brought about by improved surgical management specifically for the complicated retinal detachment the same might be included for the case of retinopexy. Even though silicone oil extraction can exhibit a number of benefits, it is necessary that these are compared to the durational extension as well as the probability that it might cause complications, particularly after a new procedure has been performed. 

There are several factors which might be linked to the functional and anatomical outcomes upon the completion of the silicone oil extractions in the proliferative vitreoretinopathy cases. It has been established that encircling peripheral and buckle photocoagulation before the process of silicone oil extraction is of advantages and proven to be healthy for the patients. From the outcomes, it could be stated that anatomical outcomes are not fully collated with the functional outcomes. This is in line with the narrative that there are no established definite explanations for the optic atrophy or vision loss after the procedures involving the silicone oil extractions. Significantly, a longer period of closer contact with the silicone oil and retina is likely to cause abnormal potassium exchanges and dysfunctional central Muller. 

Also, there are several identified avenues which can be exploited for a better insight into the application of the ROCK inhibitors specifically for the clinical trials. There is a need for the verification and ascertainment in the usefulness of these drugs for the patients. According to authors, more focus should be on the positive effects they may have and minimal side effects so that they can be used on the patients with retinal problems for the protection and prevention of complications upon the treatment completion. At 6 months of post-surgery, about 62.5% of the patients had reattached retina (Ganekal & Dorairaj, 2014). There were no significant statistics in the two studies. Therefore, the study failed to give an establishment and approval of efficacy in the use of intra-operative use where 5-FU, as well as LMWH, is applied. Again, there are no significant side effects which could be attributed to the method of treatment. Thus, the treatment can be part of the further analysis as they present less negative effects on the surgical procedures involving retinal detachments. Generally, it could be confirmed that the study failed to give a proof to the efficacy of the intraoperative use 5-FU as well as the use of LMWH in a combination in which the two substances are used as a regiment of anti-proliferation. 

However, with the inclusion of IMI treatments, it is learned that there are low PVR incidences especially during the time of RD repair (Sadaka et al., 2016). Again, it is ascertained that there is the existence of interplay among the growth factors such as the matrix protein, and other cell typologies which are responsible for the driving of the undesirable formation of the peri-retinal membranes. From this finding, there is the creation of an understanding which is potential for the aiding of the different adjusts agents which might be responsible for the block of the cellular events (Sadaka & Giuliari, 2012). 

It is necessary to put categorically that the adjuvant may be used through well-detailed research to come to terms with quality results which can help in the future treatments. From the previous studies carried out, (Townes-Anderson et al., 2017) it could be shown that vitreous enhances the degradation of the tumor protein p53. Also, it is within the context that knockdown of the phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ka and -b). MTX treatment would abrogate the proliferation of the p53-deficient cells; it is found from results that vitreous is capable of enhancing the expression in PI5P4Ka and –b within the RPE cells. It is within the same knocking down of the PI5P4Ka and -b that the abrogated vitreous stimulated cell survival, proliferation, and migration. 

It has been established through the review that PVR cells extracted from human membranes can perfectly be cultured and upon isolation after which they can be profiled (Amarnani et al., 2017). Through the analysis of these primary cultures, there is the identification of MTX which is seen as capable significantly hindering growth and enhancing the cells death of PVR cells in the vitro. Therefore, the MTX identified can be said to be of importance in reducing the growth of PVR cells hence should be used for the patients with PVR defects. Again, in the drug testing, the cultured cells can be used in the identification of the most appropriate medical intervention in case of such growth. 

Important to put into consideration is the fact that suppression of PI5P4Ka and -b abrogated pathogenesis of the PVR which is induced by the intravitreal cell among some animals such as rabbits. There were important revelations that the expression of the PI5P4Ka and –b was more pronounced and abundant at the epiretinal membrane from the PVR patients of grade C. It can be concluded based on the results derived from this study that PI5P4Ka and –b could be instrumental in the therapeutic specifications and targets for the treatment of the patients with the PVR challenges. Therefore, it calls on further research and study in line with these findings to validate the importance of PI5P4Ka and –b in the treatment of proliferative vitreoretinopathy (PVR) especially among the patients at the grade of C. It is within the same knocking down of the PI5P4Ka and -b that the abrogated vitreous stimulated cell survival, proliferation, and migration. 

In case there are failures noted in any of the approaches and treatment interventions applied in the PVR treatments, Retinectonmy is in most instances employed as the last resort. Again, if PVR is located within the inferior areas of the retina, there are about two options which can be used apart from Retinectonmy. One of the options is to apply silicone oil after the removal of membranes or there can be a combination of vitrectomy with the buckle of the external surface techniques. However, the use of silicone oil is rare and not encouraged as it is having a number of negative side effects (Papastavrou et al., 2017). Visual acuity is realized to be low because of the macular status which is linked to the presence of detachment in the entire states and activities included for the detachment. In summary, there are suggestions that the use of C 3 F 8 as a tamponade agent in conjunction with adequate prone positioning is sufficiently effective for the cases of PVR with severe statuses where Retinectonmy is involved. This is a result of functional and anatomical results borne out of such treatment procedure. Therefore, it is appropriate to infer that there can be the combined use of strategies and treatment approaches to ensure effective results and to create precedence for subsequent treatments. 

From the previous studies (Townes-Anderson, 2017), it has been concluded that vitreous elements are responsible for the stimulation of the degradation process of the tumor process suppressor proteins p53 (Ma et al., 2016). Therefore, there was a need for a study to establish the possibility that suppression of PI5P4Kα and -β would curtail vitreous induced cellular responses and proliferative vitreoretinopathy (PVR). From the results of the study where PI5P4Kα and –β is applied in the treatment, it can be concluded that PI5P4Kα and –β have a higher potential of treating PVR. Therefore, the use of such therapies which reduces the extent of growth of the unwanted cells can be the most effective considering the possibility of the side effect which is minimal. 

As a matter of statistics, it could be seen that 43.4% of the patients were seen to have an improvement in the visual acuity (Tavares et al., 2015). Again, it could be realized that 20.8% of the patients were in stable condition (Tavares et al., 2015). Unfortunately, there were eventualities as it could be seen from the study that 35.8 of the cases were having a worsening state of visual acuity. Another important statistics was that there were about 5 patients who had attached retina had no explained disc atrophy in their outcomes (Tavares et al., 2015). Thus, there need for Prophylactic treatment to reduce cases of complications. It could be realized though that this data was not significant as far as statistics for the general study is concerned. The reason for the insignificance was that there was no correlation identified between the time of duration in the PVR membrane and EMP2 expression. 

Proliferative Vitreoretinopathy (PVR) is an eye defect which develops in approximately 40%-60% of patients diagnosed with open globe injury (Morescalchi et al., 2013). The introduction of immune cells in the vitreous enhances the production of cytokines and other growth factors whose contact with intraretinal cells is likely. These cytokines and growth factors are responsible for the driving of cellular responses which leads to PVR development. Therefore, having knowledge of pathophysiological and pathobiological strategies employed in posttraumatic PVR is likely to increase the possibility of management. It is expected that in future, there should be an application of a multidrug approach which can be more effective in the recovery of visual functions. 

There are a number of approaches put in place to ensure the restoration and visual functioning in case of proliferative vitreoretinopathy (PVR). The approach of Retinectomy where C3F8 is involved as the tamponade provide anatomical restoration with 75% basic success (Papastavrou et al., 2017). In a conclusive reaction, it can be inferred that the use of C3F8 as the agent together with adequate frequency positioning can be enough in cases of severe proliferative vitreoretinopathy (PVR). Such combined treatment approaches are effective in that they provide an encouraging functional and anatomical outcome. Thus, it cannot be entirely purported that it is effective. However, with a combination of complementary approaches, there can be seen as successful results and a better treatment approach. 

There has been the requirement to find the effectiveness and plausibility of epithelial membrane 2 expressions in membranes from surgical patients with proliferative vitreoretinopathy (PVR). All the proliferative vitreoretinopathy (PVR) in their membranes shows a greater percentage of EMP2 than ERMS (Telander et al., 2016). However, there is no correlation found in the duration of proliferative vitreoretinopathy (PVR) membrane and expression of EMP2. According to the study conducted by Telander et al (2016), all the studied proliferative vitreoretinopathy (PVR) and ERMS shows EMP2. Therefore, it is rightful to conclude that the epithelial membrane 2 is responsible for the occurrence of proliferative vitreoretinopathy (PVR) especially the ones with inflammatory features. 

There are complexities presented by the molecular and biological factors which have been seen to drive the pathogenesis of PVR. There is the process which creates a sense of interplay between the growth factors such as cytokines, matrix proteins as well as various cell types which are seen as driving the unwanted formation of the periretinal membranes. Due to such understandings, as well as the noted unsuccessful rates reported about surgical procedures, there is the formation of understanding pertaining to the efficacy of various agents which might be seen as capable of creating a blockade in the cellular events seen as intrinsic to PVR. Therefore, it calls for the combination of therapies to see into it that there are satisfactory mechanisms and preventive factors of post-retinal treatment which can be used in the treatment process. 

It is apparent from eyes are subjected to risks of PVR in case there were incidences of PVR before. However, with the inclusion of IMI, it is observed that the risks are reduced particularly during the time of RD and PPV repair (Sadaka et al., 2016). The most essential factor considered in most of the treatment procedures in the medical or clinical operations is the effect of treatment itself. It calls that there is a need for the treatment procedure involved to be marked by low chances or cases of side effects which might result in the reduced efficiency. Looking at the case presented above, there are situations and treatment procedures which can be more effective particularly the use of IMI which might reduce the chances of side effects. It becomes necessary that such factors are included in the subsequent treatment procedures. 

Conclusion 

Upon the detailed secondary research and review of information from various literature and scholarly articles, it could be confirmed that Prophylactic treatment after retinal detachment surgery prevents further complications such as vitreoretinopathy. This could be validated from the various studies which have been conducted on the pre-clinical and cohort designs. However, there is a challenge given as the treatment strategy and the medication involved might result in negative effects on the patients. Important is that there are treatment methodologies which have seen close to 75% of success in their inclusion. Therefore, it can be summarized that there is a need for Prophylactic treatment so as to prevent the emergence of complications. Important is that it had a significant impact on cell migration (Amarnani et al., 2017). From findings, it could be concluded that proliferative vitreoretinopathy cells obtained from human membranes can be profiled, cultured and isolated in vitro 

References 

Amarnani, D., Machuca-Parra, A. I., Wong, L. L., Marko, C. K., Stefater, J. A., Stryjewski, T. P., ... & Kim, L. A. (2017). Effect of methotrexate on an in vitro patient-derived model of proliferative vitreoretinopathy.  Investigative Ophthalmology & Visual Science ,  58 (10), 3940-3949. 

Falavarjani, K. G., Hashemi, M., Modarres, M., & Khani, A. H. (2014). Intrasilicone oil injection of bevacizumab at the end of retinal reattachment surgery for severe proliferative vitreoretinopathy.  Eye ,  28 (5), 576 

Ganekal, S., & Dorairaj, S. (2014). Effect of intraoperative 5-fluorouracil and low molecular weight heparin on the outcome of high-risk proliferative vitreoretinopathy.  Saudi Journal of Ophthalmology ,  28 (4), 257-261. 

Ma, G., Duan, Y., Huang, X., Qian, C. X., Chee, Y., Mukai, S., ... &D'Amore, P. A. (2016). Prevention of proliferative vitreoretinopathy by suppression of phosphatidylinositol 5-phosphate 4-kinases.  Investigative Ophthalmology &Visual Science ,  57 (8), 3935-3943. 

Morescalchi, F., Duse, S., Gambicorti, E., Romano, M. R., Costagliola, C., & Semeraro, F. (2013). Proliferative vitreoretinopathy after eye injuries: an overexpression of growth factors and cytokines leading to a retinal keloid.  Mediators of Inflammation ,  2013 . 

Papastavrou, V. T., Chatziralli, I., & McHugh, D. (2017). Gas Tamponade for Retinectomy in PVR-Related Retinal Detachments: A Retrospective Study.  Ophthalmology and Therapy ,  6 (1), 161-166. 

Sadaka, A., & Giuliari, G. P. (2012). Proliferative vitreoretinopathy: current and emerging treatments.  Clinical Ophthalmology (Auckland, NZ) ,  6 , 1325. 

Sadaka, A., Sisk, R. A., Osher, J. M., Toygar, O., Duncan, M. K., & Riemann, C. D. (2016). Intravitreal methotrexate infusion for proliferative vitreoretinopathy.  Clinical Ophthalmology (Auckland, NZ) ,  10 , 1811 

Tavares, R. L. D. P., Nóbrega, M. J., Nóbrega, F. A. J., De Novelli, F. J., & De Oliveira, C. A. C. (2015). Timing and outcomes after silicone oil removal in proliferative vitreoretinopathy: a retrospective clinical series.  International Journal of Retina and Vitreous ,  1 (1), 2. 

Telander, D. G., Alfred, K. Y., Forward, K. I., Morales, S. A., Morse, L. S., Park, S. S., & Gordon, L. K. (2016). Epithelial membrane protein-2 in human proliferative vitreoretinopathy and epiretinal membranes.  Investigative Ophthalmology &Visual Science ,  57 (7), 3112-3117. 

Townes-Anderson, E., Wang, J., Halasz, E., Sugino, I., Pitler, A., Whitehead, I., & Zarbin, M. (2017). Fasudil, a clinically used ROCK inhibitor, stabilizes rod photoreceptor synapses after retinal detachment.  Translational Vision Science &Technology ,  6 (3), 22-22 

APPENDIX 

Table 1: Evidence Table 

First Author	Date of Publication	Study Design	Level  of Evidence	Study Population	Therapy or Exposure	Outcome/ Results
K GhasemiFalavarjani	February 21, 2014	Pro-spective	3	Patients with grade C Retinal detachment	In the study group, 1.25 mg bevacizumab was injected into the silicone oil prior to closure of surgery.	Retinal redetachments were observed in nine out of thirty-eight patients. As well as extensive subretinal fibrous proliferations were seen in the study group.
Renata Leite De Pinho Tavares	April 15, 2015	Retro-spective	3	Patients with retinal detachment followed after silicone oil removal	Peripheral laser photocoagulation performed to participant patients prior to removal of silicone oil. Outcomes divided into stability, worsening, or improvement.	Post silicone oil extraction showed good anatomical outcomes. Silicone extraction may be used to a new surgical procedure.
David G. Telander	February 29, 2016	Cohort	3	Preretinal membranes from patients with proliferative vitreoretinopathy (PVR) and Epiretinal membranes (ERMs)	Preretinal membranes were induced to evaluate the expression of EMP2- epithelial membrane protein-2	EMP2 were expressed in both ERMs and PVR membranes. In all PVR the expressions were significantly higher than in ERMs. This information can be used in the treatment plan in patients with PVR.
AmaSadaka	September 19, 2016	Cohort	3	Patients with recurrent PVR	Twenty-nine eyes with recurrent PVR were treated with intravitreal methotrexate infusion (IMI)	Visual acuity corrected was observed in patients who underwent with the test in the span over six months. Retinas remained attached after IMI. Overall, the low incidence of PVR post IMI procedure with minimal safety issues.
Dhanesh Amarnani	May 30, 2017	Cohort	3	Patients with Grade C PVR going under surgery for retinal repair	Methotrexate (MTX) was used on a patient who underwent retinal repair with PVR.	Cell cultures obtained from the subject patients were used to assess the effect of methotrexate on the proliferation, migration, and cell death. With the use of methotrexate, a significant reduction was used in the formation of the band in the process of retinal detachment. But, there was no significant effect on cell migration. There were increased caspase-3/7 indicating induction of regulated apoptosis.
Ellen Townes-Anderson	May 8, 2017	Pre-clinical	0	Retinal Pigs	Retinal detachments were performed in pigs by injecting a balanced salt solution (BSS) along with fasudil.	Using fasudil in inhibiting Rho kinase (ROCK) reduced the retraction of the rod by 51.3% compared to the control group. Inhibition of ROCK maintained the rod-bipolar synapse and reduced degeneration of photoreceptor after retinal detachment.
Sunil Ganekal	March 11, 2014	Case-control	3	Patients that are high-risk of retinal detachment with proliferative vitreoretinopathy	Intraoperative 5-fluorouracil (5-FU)and low molecular weight heparin (LMWH) were used during the vitrectomy in study group patients. On the other hand, the control group went through the same style of vitrectomy but without the use of 5-FU and LMWH	Six months post surgery, data were re-evaluated which showed 62.5% of patients had successful reattachment of the retina. But, statistically, the difference between both groups’ success outcome was insignificant. Also, complications and drug adverse effects between both groups were not significant.
Gaoen Ma	June 9, 2016	Pre-clinical	0	Humans ARPE-19 cells	PI5P4Ka and B were knocked out from the ARPE-19 cells	Cell proliferation, survival, migration, and contraction repealed when PI5P4Ka and B were knocked out. PI5P4Ka and B is useful in therapeutic treatments with patients who have proliferative retinal vitreoretinopathy
Vasileios T. Papastavrou	February 3, 2017	Retro-spective	3	Proliferative vitreoretino-pathy with retinal detachment	Retinectomy with use of C3F8- perfluoro-octane gas	The use of C3F8 has shown great results with 75% of success rate involving the restoration of anatomical and functional vision in patients with complications in retinal detachment.
Steven Pennock	January 4, 2013	Pre-clinical	0	PVR-positive rabbit eyes	Ranibizumab (RBZ) targeting vascular endothelial growth factor A (VEGF-A)	Using RBZ protected tested rabbits from developing proliferative vitreoretinopathy.