Proliferative vitreoretinopathy (PVR) is the most common cause of why surgical repairs of rhegmatogenous retinal detachments fail.1 The incidence of PVR in all cases of rhegmatogenous retinal detachments is estimated to be 5 to 10%.1
PVR is an abnormal wound healing response where there is formation and contraction of proliferative cellular membranes in the vitreous cavity and on both sides of the retinal surface.
It is important for optometrists to be knowledgeable about PVR because contraction of these cellular membranes can cause the retina to re-detach and transform a rhegmatogenous detachment into a tractional retinal detachment.2
Pathophysiology of PVR
Two processes occur that act as the precipitating factors of a potential PVR when a rhegmatogenous retinal detachment occurs: breakdown of the blood-retinal barrier and retinal hypoxia.
Breakdown of the blood-retinal barrier (BRB)
After a rhegmatogenous retinal detachment occurs, the change in the interface between the outer retina and the retinal pigment epithelium (RPE) can trigger the migration of RPE and glial cells onto the retinal surface and into the vitreous cavity.1,2,3
This intricate process causes the BRB to become disrupted, leading to an inflammatory response where there is an influx of cytokines and tissue growth factors from systemic circulation that eventually interact with various RPE and glial cells to drive further local production of cytokines and tissue growth factors into the vitreous cavity.1,2,3
Once the event of cell proliferation and migration occurs on the retinal surface and in the vitreous cavity, the RPE, glial cells, cytokines, tissue growth factors, and other inflammatory markers can transform into membranes and become fibroblast-like cells that have the ability to contract.1,2,3
Retinal hypoxia
After separation of the retina in a rhegmatogenous retinal detachment, the outer retinal layers become ischemic from the breakdown of the BRB and then the process of apoptosis is induced, wherein photoreceptors undergo oxidative stress contributing to photoreceptor cytotoxicity and eventual cell death.1,2,3
Risk factors related to PVR
Numerous risk factors for PVR have been established, including:4,5
- Large or multiple retinal tears
- Vitreous hemorrhage
- Choroidal detachment
- Eye trauma
- Multiple past ocular surgeries
- Cigarette smoking
Clinical presentation of PVR
Diagnosis of PVRs are similar to diagnosing retinal detachments: A dilated fundus exam and scleral depression should be performed to view details of the retina, B-scan ultrasonography can be done to determine the location and the severity of the retinal detachment.
This is particularly helpful if the view of the retina is obscured by blood or dense cataracts, and optical coherence tomography (OCT) can be used to assess if the macula or other retinal areas are also detached.6,7
The clinical presentation of PVR is specifically defined by fixed retinal folds from the traction of retinal membranes.6,7,8 Fixed retinal folds will usually localize inferiorly due to gravity, appear as wavy or rippling, and often present with haze and pigment in the vitreous cavity.6,7,8 The presentation of fixed retinal folds is how PVR and a primary rhegmatogenous retinal detachment can be differentiated.
There is minimal to no movement of the retina during eye movements in patients with PVR, while eyes with a primary rhegmatogenous retinal detachment without PVR will show an evident bouncing movement of the retina during eye movements.6.7,8
Figure 1: Widefield color fundus photograph of retinal detachment with wrinkling of the retinal surface and multiple retinal breaks seen temporally.
Figure 1: Proliferative vitreoretinopathy©Manish Nagpal et al. Image used under CC BY 4.0.
Considering other causes of PVR
When assessing for PVR, it is imperative to consider other causes for proliferative and contractional retinal conditions, such as:6,7,8
- Proliferative diabetic retinopathy
- Proliferative ischemic retinopathy
- Proliferative sickle cell retinopathy
- Retinal detachments from ocular trauma or an intraocular foreign body
Surgical intervention for PVR
The main treatment for retinal detachments with PVR is surgical intervention. Surgical intervention commonly involves the combination of a vitrectomy, membrane peel, and scleral buckle in order to reduce peripheral retinal traction and promote flattening and reattachment of the retina.6,7,8
However, the presence of retinal membranes and intraretinal fibrosis in more severe cases of PVR requires additional procedures to relieve the retinal traction in order to reattach the retina and prevent re-detachment of the retina.6,7,8
Figure 2: Widefield color fundus photograph of retinal detachment with multiple areas of intraretinal and subretinal fibrosis suggestive of PVR changes.
Figure 2: PVR changes©Manish Nagpal et al. Image used under CC BY 4.0.
Currently, the timing of surgery for PVR is controversial. Some propose to delay surgical intervention by a few weeks because the trauma induced by additional surgery could stimulate additional cellular membrane proliferation.
However, the implications on visual recovery if the macula is involved must also be considered when deciding to delay surgery.8,9 Of note, 10 to 40% of retinal detachments with PVR remain attached despite repeated surgery attempts.
Even with surgical success, patients can have poor visual outcomes due to the possibility of macular changes post-surgery, such as macular pucker formation, cystoid macular edema, and subretinal fibrosis.8,9
Utilizing silicone oil as a tamponade agent
Silicone oil (SO) remains an essential intraocular tamponade for the management of complex retinal detachments complicated by proliferative vitreoretinopathy.
First introduced in 1962 by Cibis et al., SO offers several advantages over gas tamponades, including long-term stability, independence from post-operative positioning, and suitability for inferior detachments or patients unable to maintain specific head positions.10
Composed of siloxane polymers, SO is available in varying viscosities—most commonly 1,000 cs and 5,000 cs—with the latter being more resistant to emulsification but more difficult to handle surgically.11
Clinical evidence from a recent retrospective series demonstrates that SO tamponade achieves high rates of anatomic reattachment (84 to 86%) and meaningful visual recovery, with longer intraocular duration (~9 to 10 months) associated with lower rates of recurrent detachment after oil removal.12
Despite its effectiveness, prolonged SO tamponade carries risks including cataract formation, intraocular pressure elevation, corneal decompensation, and emulsification, all of which underscore the importance of individualized management and meticulous surgical technique.
Ultimately, SO remains a critical tool in the vitreoretinal surgeon’s armamentarium, providing durable anatomic stabilization and functional vision restoration in eyes with PVR when used judiciously and removed at an appropriate interval.11,12
What is on the horizon for treatments for PVR?
There are several treatments for PVR that are currently being researched with promising results.
Intravitreal methotrexate
Methotrexate is a folate antagonist, which promotes anti-proliferative activity by reducing DNA replication and cell proliferation, and anti-inflammatory activity by stimulating adenosine release.13
In vitro studies on PVR membranes isolated from human patients have revealed that methotrexate could decrease RPE cells proliferation and migration, thus reducing an overall inflammatory response.13
5-fluorouracil (5-FU)
5-fluorouracil is an anti-proliferative agent and Blumenkranz et al. demonstrated that 5-FU reduced tractional retinal detachment in PVR animal models and was well tolerated in the posterior segment as part of vitreoretinal surgery.14,15
Steroids
The efficacy and influence of steroids for reducing the incidence of PVR after rhegmatogenous retinal detachment surgery remain controversial. Studies completed by Xu et al. revealed that rhegmatogenous retinal detachment surgery combined with the administration of steroid drugs could significantly reduce the recurrence of PVR and macular edema after surgery.16
Amniotic membranes
Human amniotic membranes are extraembryonic tissues currently employed in the treatment of many ocular diseases.17 Several reports conducted by Caporossi et al. indicated that amniotic membranes can inhibit the signaling pathway of certain inflammatory markers, such as tissue growth factors and cytokines, that are known to play a major role in the pathogenesis of PVR.17
Moving forward, a better understanding of the pathogenic process of PVR may result in a better selection of therapeutic targets that affect how the retina responds to inflammation. Larger clinical trials are required to better assess effective adjunctive treatment options in combination with surgery for the proper treatment and management of PVR.
Co-managing proliferative vitreoretinopathy
The relationship between optometrists and ophthalmologists is important when co-managing a patient with PVR. This is because optometrists play a critical role in initially diagnosing a patient with PVR and then immediately referring the patient to a retina ophthalmologist for necessary pharmacological and surgical intervention.
The retina specialist will manage the treatments and post-operative care and then communicate major findings back to the optometrist for appropriate ongoing monitoring.
Harris Ahmed, DO, MPH, is a vitreoretinal surgery fellow physician at Weill Cornell.
What clinical findings should prompt an optometrist to refer a patient to an ophthalmologist for PVR?
PVR typically develops as a complication of retinal detachment or following retinal surgery.
Optometrists should refer urgently if they see signs of:
- Recurrent or persistent retinal detachment
- Membranes on the retinal surface
- Retinal folds
- Fixed retinal corrugations
- Star folds
- Vitreous haze suggesting proliferative activity
In the right clinical context, even seeing pigment clumps in the vitreous is part of the PVR spectrum. Progressive vision loss, distortion, or a redetachment after prior surgery are all red flags. Essentially, any evidence that the retina is not lying smoothly after a repair—or suspicion of tractional forces developing—should prompt referral.
Of note, uveitis/retinitis, significant horseshoe tears, and extensive laser can lead to the PVR spectrum as well. It is also important to note that there may be patients who have chronic, demarcated retinal detachments that have been observed for months or years. In these patients, although the detachment may appear stable, if PVR is noted, that may change follow-up and management.
What diagnostic imaging should be performed and provided for PVR?
Fundus photography with OCT capability (i.e., Optos with widefield OCT) and macular OCT are most useful for documenting and communicating findings. OCT can reveal epiretinal or subretinal membranes and macular distortion, while widefield imaging helps demonstrate the extent of detachment or fibrous proliferation.
B-scan ultrasonography is valuable if there is media opacity, such as vitreous hemorrhage or cataract, that obscures the view. Sending these images to the retina specialist helps establish the baseline and speeds up management decisions.
How can ODs best educate on typical PVR treatment protocols to help prepare patients and manage expectations?
Patients should be informed that PVR commonly requires surgical management—often repeat pars plana vitrectomy, typically combined with membrane peeling, retinectomy, or scleral buckle, and use of long-acting tamponade such as silicone oil.
It is important to set expectations: these are complex, multi-step surgeries with lower anatomic and visual success rates compared to primary retinal detachment repair.
Multiple surgeries may be necessary, and vision may remain limited even with successful reattachment. Patients should also understand the importance of strict adherence to positioning and follow-up instructions after surgery.
If they are in the early stages of PVR or not yet requiring surgical intervention, the patient should be informed that they require close follow-up and that there are some modified treatment protocols that may help, such as intravitreal methotrexate injections.
Some surgeons administer methotrexate intra-operatively or in serial injections post-operatively. Other agents under investigation include 5-fluorouracil (5-FU), daunorubicin, and corticosteroids.
While these treatments are still evolving, patients may benefit from knowing that adjunctive medical therapies exist to try to limit recurrence. Appropriately framing emerging treatments is critical in maintaining public trust and patient expectations.
What potential complications should ODs be aware of and how should they be handled?
The natural course of PVR carries a high risk of recurrent detachment, hypotony, and proliferative traction.
Post-operatively, patients with PVR may develop:
- Elevated intraocular pressure (IOP)
- Cataract progression
- Silicone oil–related complications (ex., secondary glaucoma, corneal decompensation, and band keratopathy)
- Rarely endophthalmitis
Optometrists should refer urgently if a patient presents with sudden pain, new redness, vision loss, or changes in the red reflex. While methotrexate injections are generally well tolerated, they can cause mild corneal epitheliopathy, which ODs may pick up during routine follow-up exams.
Do you have tips for long-term co-management?
In co-managing these patients, ODs should monitor IOP, lens status, and corneal health, particularly in eyes filled with silicone oil. OCT and serial fundus photography can be used to track structure once media clarity allows.
Systemic disease control (diabetes, hypertension, and smoking cessation) remains important, especially in patients with high-risk fellow eyes. Regular updates to the retina specialist, particularly about IOP and visual function, help optimize care. Having a low threshold for re-referral or earlier follow-up is very reasonable and preferred.
Are there any common mistakes you see optometrists make when co-managing PV?
Again, we are grateful our optometry colleagues are helping us follow and manage these complex patients. The biggest mistakes include delaying referral when new folds or traction are suspected, assuming a “quiet” appearance equals stability, and giving overly optimistic expectations about vision recovery.
Another common oversight is failing to monitor for silicone oil–related issues or complications from adjunctive intravitreal medications, such as corneal toxicity from methotrexate. Vigilance in follow-up and communication with the surgeon prevents small problems from escalating.
These mistakes happen to all of us, and are not unique to our optometry colleagues, who are often the first line or primary care physician (PCP) of the eye.
Key takeaways
- PVR is a multifactorial and complex condition that is the main cause of why surgical repairs of rhegmatogenous retinal detachments fail.
- PVR pathophysiology involves the breakdown of BRB and retinal hypoxia.
- The clinical presentation of PVR is defined by fixed retinal folds from the traction of retinal membranes.
- Though several different surgical techniques have been studied and taught to improve the visual prognosis in patients with PVR, outcomes are still considered unsatisfactory. Due to this, various adjunctive treatment options have been investigated in clinical studies.
- Because optometrists play a critical role of initially diagnosing a patient with PVR, the co-management relationship between optometrists and ophthalmologists is an important one in the success of appropriately treating PVR patients.
Closing thoughts
In summary, proliferative vitreoretinopathy remains the leading cause of failure in rhegmatogenous retinal detachment repair, underscoring the importance of vigilance among optometrists in early recognition and referral.
A clear understanding of its complex pathophysiology, risk factors, and clinical presentation allows for timely diagnosis and appropriate co-management with retina specialists. While surgical intervention remains the cornerstone of treatment, emerging adjunctive therapies hold promise in improving outcomes.
Ultimately, optometrists play a vital role in both the detection and long-term monitoring of PVR, making interdisciplinary collaboration essential to optimizing patient care.
