**8. Surgery vs. observation**

On the other hand, although postoperative visual field loss is known to occur in some cases following ERM surgery, its correlation with anatomical changes in the OCT has not been confirmed by the literature. The effect of surgery on the nerve fibre layer (NFL) and the ganglion cell layer (GCL) are under intense investigation, especially with "*en face*" OCT and other sophisticated techniques. However, the results on whether there is loss of neuronal or glial tissue remain ambiguous, as do reasons for the late deformation of the central retina, often observed following ERM surgery. Based on modern retinal imaging modalities, it is believed

Secondary epiretinal membranes have worse prognosis than idiopathic membranes [69]. Limited visual recovery, as well as higher recurrence rates, is reported. Diabetic membranes are difficult to manage, as they are accompanied by severe retinal damage that can lead to serious complications including haemorrhage, detachment and re-proliferation of the connec‐ tive tissue [87]. Postoperative ERMs (including ERMs developed after vitrectomy for retinal detachment, but also after laser or cryo-retinopexy) have limited visual recovery, especially when the macula is detached [88]. Finally, inflammatory membranes illustrate variable results, depending mostly on the effect of the subjacent inflammation on the retinal function [89].

Epiretinal membrane removal is generally a safe procedure. Intraoperative complications involve retinal breaks, retinal haemorrhage, retinal whitening and retinal surface damage. Postoperative complications include cataract formation, rhegmatogenous retinal detachment (RRD), cystoid macular oedema, endophthalmitis and the recurrence of fibrotic tissue.

A common intraoperative complication is the creation of iatrogenic retinal breaks. These occur during vitrectomy; thus, careful examination of the periphery with indentation at the conclu‐ sion of surgery is crucial for their early/prompt diagnosis. Their treatment is straightforward, that is, through the application of intraoperative laser retinopexy or cryopexy. However, a break can also occur at the posterior pole (due to pinching or during the dissection of a highadherent membrane) and in this case, laser treatment may be hazardous to the fovea and

Haemorrhage at the site of pinching or grasping or at the area where the membrane detaches from a retinal vessel is also common. In this case, recovery is usually short and uneventful. More extensive bleeding may occur less often when a vessel is damaged during the dissection

Retinal whitening is the result of ischaemia that usually resolves intraoperatively; nevertheless, sometimes it may persist for an extended period of time. Membrane manipulation can also cause surface tissue damage, which may or may not be symptomatic. Symptoms involve primarily visual field defects and one should differentiate if these are due to tissue deficits or

and can be controlled by increasing intraocular pressure or intraoperative cautery.

that retinal reconstruction continues for months after ERM peeling [85-86].

**6.3. Prognosis of different ERM subtypes**

**7. Complications**

126 Advances in Eye Surgery

should be performed with caution.

Despite the favourable results of surgery for the treatment of ERM, debate remains regarding a preferable treatment strategy. Decision for surgery and selection of the proper method depends on the surgeon's preference and on the patients' characteristics. Nevertheless, it is highly significant to perform meticulous patient selection for each method in order to achieve better outcomes with regard to patients' overall visual ability and quality of life.

As discussed above, interventional studies indicate that early surgical removal can relieve disturbing symptoms and stabilize vision, which may worsen later [74-77, 81-82]. This is in contrast with the fact that ERMs do not always progress and may be stable during follow-up without any intervention [35, 98]. Moreover, there are possible side effects to surgery and the improvement in visual acuity is greater in patients with preoperative lower visual acuity.

In the paragraphs that follow, we will attempt to review data from the literature concerning surgery timing and patient selection.

Epidemiological population-based studies suggest that a large percentage of cases diagnosed with ERM may remain stable during follow-up. These studies agree that the disease is nonprogressive in a significant percentage of cases and also that regression may be observed without any intervention. In the Blue Mountains eye study, 28.6% of cases experienced progression, 38.8% of eyes remained stable and 25.7% of cases regressed in a five-year followup period [35]. In a prospective cohort study of 1932 patients undergoing cataract surgery, it was reported that 43% of patients progressed postoperatively after one month had passed during a 36-month follow-up, 32.4% of patients remained stable and 24.6% of patients regressed [98]. According to these results, similar percentages of patients with cellophane maculopathy and patients with preretinal fibrosis progressed; additionally, the regression rates in both groups were similar: 26% of cellophane reflex cases and 18% of preretinal fibrosis cases regressed spontaneously without surgical intervention. Of the 14 cases of preretinal fibrosis regression, five cases had complete regression, while the rest had partial ERM regression. In the Blue Mountains study, regression rates were similar in the cellophane macular reflex (CMR) group and in the preretinal macular fibrosis (PMF) group (25.7% and 25.8%, respectively). Regarding progression, 16.1% of participants with PMF at baseline and 32.8% of patients with CMR at baseline progressed, including 17 eyes in which CMR pro‐ gressed to PMF (9.3%). There was no significant association between the ocular and systemic risk factors detected for predicting the progression of preretinal macular fibrosis during the five-year follow-up [35]. It appears that according to these prospective cohort studies, progression of ERM affected about a third of patients; furthermore, a small amount of patients regressed completely. The differences in percentages among studies can be attributed to the different criteria selected for progression and regression, as well as to the different study populations.

Based on these data, a follow-up period prior to making a decision for surgery was imposed in most cases, depending on the amount of visual disturbance upon diagnosis.

Regarding visual acuity, in the Blue Mountains study, the authors demonstrated that the level of mean visual acuity was only slightly affected by incident preretinal macular fibrosis and was unaffected by incident cellophane macular reflex. The average reduction of visual acuity after five years in the worst eyes was 5.7 letters (CI, 5.3 to 6.1) in subjects without incident epiretinal membranes, 7.4 letters (CI, 4.7 to 10.1) in eyes with incident preretinal macular fibrosis and 2.8 letters (CI, 1.6 to 4.0) in eyes with incident cellophane macular reflex. Corresponding mean differences in visual acuity between the baseline and a fiveyear examination were not statistically significant [35]. Thus, surgery was not promptly needed with regard to visual acuity, since the progression of vision loss, if any, was very slow. When surgery is undertaken in cases with significantly impaired visual acuity, it provides improvement more frequently and to a greater extent than in eyes with better preoperative visual acuity [79].

On the other hand, eyes with lower preoperative visual acuity tend to have lower final visual acuity, whereas the final visual prognosis is better for eyes with better preoperative visual acuity [79, 99]. Studies using spectral domain optical coherence tomography have shown that visual disturbance induced by ERM is associated with intraretinal changes, including the disruption of photoreceptor integrity. These findings suggest that the damage resulting from ERMs is partially irreversible, regardless of surgical management. Consequently, from this point of view, an early intervention prior to the induction of permanent damage seems more rational.

In order to make the decision for undergoing surgery, it is important to evaluate the prognosis of surgery in each case. Preoperative evaluation with time-domain OCT (TDOCT) and spectraldomain OCT (SDOCT) has given us the ability to assess morphologic features that correspond to intraretinal tissue damage and its association with preoperative visual symptoms, and to evaluate the potential for improvement [81, 100-103]. According to clinical studies with TDOCT and SDOCT, the preoperative disruption of the photoreceptors' inner and outer segment junction (ellipsoid zone, IS/OS) is one of the main prognostic factors. Suh et al. and Falkner-Radler et al. compared TDOCT in ERM patients pre- and post- vitrectomy and found that eyes experiencing disruption of the ellipsoid zone had significantly lower postoperative best corrected visual acuity (BCVA) and lower BCVA differences when comparing pre- and post-surgery conditions, compared to those without preoperative OCT disruption [81, 100]. The latter study additionally confirmed the predictive value of ellipsoid zone integrity for postoperative functional outcomes with SDOCT [100]. Inoue et al. and Kim et al. prospectively allocated their patients based on preoperative ellipsoid zone integrity in groups of intact versus disrupted and found that the intact ellipsoid zone cohort had better final visual acuity and better improvement in visual acuity. The predictive role of the preoperative central foveal thickness, the presence of a macular pseudohole or the presence of retinal cysts was not confirmed in these studies [101-103].

Other factors that may predict visual outcome and affect decisions regarding surgery are the presence of any other macular co-morbidity such as age-related maculopathy. The length of the photoreceptor outer segment and the thickness of the inner retinal layer are also correlated with visual function, and might therefore be useful in predicting surgical outcomes [103]. Additionally, as mentioned earlier, the presence and severity of metamorphopsia has also been correlated with final visual outcomes [81-82].

## **9. Conclusion**

progressive in a significant percentage of cases and also that regression may be observed without any intervention. In the Blue Mountains eye study, 28.6% of cases experienced progression, 38.8% of eyes remained stable and 25.7% of cases regressed in a five-year followup period [35]. In a prospective cohort study of 1932 patients undergoing cataract surgery, it was reported that 43% of patients progressed postoperatively after one month had passed during a 36-month follow-up, 32.4% of patients remained stable and 24.6% of patients regressed [98]. According to these results, similar percentages of patients with cellophane maculopathy and patients with preretinal fibrosis progressed; additionally, the regression rates in both groups were similar: 26% of cellophane reflex cases and 18% of preretinal fibrosis cases regressed spontaneously without surgical intervention. Of the 14 cases of preretinal fibrosis regression, five cases had complete regression, while the rest had partial ERM regression. In the Blue Mountains study, regression rates were similar in the cellophane macular reflex (CMR) group and in the preretinal macular fibrosis (PMF) group (25.7% and 25.8%, respectively). Regarding progression, 16.1% of participants with PMF at baseline and 32.8% of patients with CMR at baseline progressed, including 17 eyes in which CMR pro‐ gressed to PMF (9.3%). There was no significant association between the ocular and systemic risk factors detected for predicting the progression of preretinal macular fibrosis during the five-year follow-up [35]. It appears that according to these prospective cohort studies, progression of ERM affected about a third of patients; furthermore, a small amount of patients regressed completely. The differences in percentages among studies can be attributed to the different criteria selected for progression and regression, as well as to the different study

Based on these data, a follow-up period prior to making a decision for surgery was imposed

Regarding visual acuity, in the Blue Mountains study, the authors demonstrated that the level of mean visual acuity was only slightly affected by incident preretinal macular fibrosis and was unaffected by incident cellophane macular reflex. The average reduction of visual acuity after five years in the worst eyes was 5.7 letters (CI, 5.3 to 6.1) in subjects without incident epiretinal membranes, 7.4 letters (CI, 4.7 to 10.1) in eyes with incident preretinal macular fibrosis and 2.8 letters (CI, 1.6 to 4.0) in eyes with incident cellophane macular reflex. Corresponding mean differences in visual acuity between the baseline and a fiveyear examination were not statistically significant [35]. Thus, surgery was not promptly needed with regard to visual acuity, since the progression of vision loss, if any, was very slow. When surgery is undertaken in cases with significantly impaired visual acuity, it provides improvement more frequently and to a greater extent than in eyes with better

On the other hand, eyes with lower preoperative visual acuity tend to have lower final visual acuity, whereas the final visual prognosis is better for eyes with better preoperative visual acuity [79, 99]. Studies using spectral domain optical coherence tomography have shown that visual disturbance induced by ERM is associated with intraretinal changes, including the

in most cases, depending on the amount of visual disturbance upon diagnosis.

populations.

128 Advances in Eye Surgery

preoperative visual acuity [79].

Vitrectomy and membrane peeling is currently the preferred surgical treatment option for eyes with ERM. However, no consensus has been established concerning an optimal time for surgery. Early intervention may prevent the evolvement of non-reversible damage to the outer retina; however, ERM progression concerns only a small percentage of patients. Follow-up with SDOCT and clinical examination for recording visual acuity and metamorphopsia is imposed in early cases prior to decision-making. Moreover, in more advanced stages, the application of SDOCT for assessing retinal integrity and predicting postoperative outcomes is necessary in order to predict possible functional gain following surgery.
