- Stage 3 – Extraretinal fibrovascular proliferation (EPF): EPF or neovascularization extends from the ridge into the vitreous. It is continuous with the posterior aspect of the ridge (Figure 5). It is further subdivided into mild, moderate or severe depending on the extent of EPF infiltrating the vitreous.
Figure 5: Retcam picture of RE showing stage 3, ridge (black arrow) and extra retinal fibrovascular proliferation (white arrow).
- Stage 4 – Partial retinal detachment: Stage 4 is divided into partial retinal detachment not involving fovea, stage 4A (figure 6) and involving fovea, stage 4B. Visual prognosis of stage 4B is poorer than 4A.
Figure 6: Retcam picture of LE showing stage 4A partial retinal detachment (black arrow) in the temporal periphery not involving fovea.
- Stage 5: Total retinal detachment: These retinal detachments are generally tractional and may occasionally be exudative. Visual prognosis is the worst for stage 5 ROP (Figure 7).
Figure 7: Retcam picture showing leucokoria (white arrow) secondary to total retinal detachment with funnel shaped total retinal detachment on B scan
- Aggressive posterior ROP (AP-ROP): An uncommon, rapidly progressing, severe form of ROP is designated AP-ROP. If untreated, it usually progresses to stage 5 ROP. The characteristic features of AP-ROP are its posterior location, prominence of plus disease, and it does not follow the stages mentioned above(Figure 8). It is observed most commonly in zone I, but may also occur in posterior zone II.
- Plus disease: It is an additional sign indicating the severity of active ROP. This includes increased venous dilaattion and arteriolar tortuosity of the posterior retinal vessels (Figure 9) and may later increase in severity to include iris vascular engorgement, poor pupillary dilatation (rigid pupil), and vitreous haze.
Figure 8: Fundus picture of LE showing AP-ROP.
Figure 9: Fundus picture of RE showing venous dilatation (black arrow) and arteriole tortuosity (white arrow) signifying plus disease.
- Pre-plus disease: It is defined as vascular abnormalities of the posterior pole that is insufficient for the diagnosis of plus disease but demonstrates more arterial tortuosity and more venous dilatation than normal.
Figure 10: Drawing scheme for ROP.
Management of ROP
When to treat?
- Threshold disease: It was defined by the CRYO-ROP study,5 as Stage 2 in zone I or II involving > 5 contiguous or 8 cumulative clock hours with plus disease. This was the previous “cut off” stage for treatment.
- Prethreshold Disease: Early Treatment ROP (ETROP) study6 has revised the treatment guidelines. This study proved that earlier treatment (Pre Threshold stage) has a better outcome. They divide prethreshold ROP into
- High Risk Prethreshold or Type 1 ROP: This is the new “cut off” for treatment. It should be treated immediately. It is defined as
- Zone 1 any stage with plus disease or
- Zone 1 stage 3 without plus disease or
- Zone 2 stage 2 or 3 with plus disease.
- Low Risk Prethreshold Disease or Type 2 ROP: These eyes should be considered for treatment only if they progress to type 2 or threshold ROP. It is defined as
- Zone 1 stage 1 or 2 without plus disease or
- Zone 2 stage 3 without plus disease.
How to treat?
Principle is ablation of the ischemic peripheral retina stops release of angiogenic factors. Two options are available:
- Cryotherapy: Involves placing a very cool probe on the sclera and freezing, until an ice ball is formed on the retina inside. Multiple applications are made to treat entire avascular retina anterior to the ridge (Figure 11). However cryotherapy has a lot of disadvantages. It requires general anesthesia, has more local complications like severe lid edema and for zone I cases, the cryo probe cannot reach posteriorly because of the restriction caused by the conjunctival fornix.
Figure 11: Schematic diagram of fundus showing multiple white cryo burns (black arrows) in avascular retina anterior to ridge (white arrow).
- Laser Photocoagulation: It is a practical alternative after the advent of indirect laser delivery system. Direct treatment of retina from inside, so less local inflammation. The main advantages are that it can be performed under topical anesthesia, systemic and local complications are much less compared to cryotherapy, and it can be done as out patient procedure and posterior retina in zone I cases can be treated easily (Figure 12). Diode red (810 nm) is the laser of choice. However green laser (532 nm) laser can also be used.
Video : Diode laser photocoagulation (Click right and select rewind to see the video from begining)
Figure 12: Fundus picture of RE showing laser scars (black arrows).
Laser or cryotherapy can only be done till stage 3 ROP. Management of stages 4 and 5 is surgical and final outcome is very poor for these stages.
- Surgical treatment: Surgery is advocated if laser or cryotherapy is unsuccessful in preventing progression to stage 4 or 5. Surgical options available are
- Scleral buckling
- Lens sparing vitrectomy for stage 4
- Lensectomy + vitrectomy
- Open sky vitrectomy for stage 5
In our series7, anatomical success was 90% (9/10) for stage 4A, 44.4% (4/9) for stage 4B, and 14.3% (2/14) for stage 5 ROP. Overall anatomical success was 45.4% (15/33 eyes). Our study has shown poor results as regard to the anatomical outcome following surgery for stages 4 & 5 ROP. This just reemphasizes the need for increasing awareness, having effective screening programmes, timely referral and appropriate intervention.
ROP management doesn’t end with laser or surgery. Once treated, lifelong followup (yearly) is mandatory. All other premature infants irrespective of having ROP yearly followup till the age of 5 years is advisable to rule out refractive errors (most common), squint and amblyopia.
Role of anti VEGF injections in ROP:
- Very controversial
- For normal vascularization of the retina to be completed, VEGF is needed in these premature infants.
- Thus anti VEGF injections will stop growth of not only abnormal new vessels but also the normal ones.
- Also systemic absorption may cause vascular development delay in other organs developing also.
- Currently anti-VEGF injections are used in ROP only when the standard treatment (which is laser) fails and the disease progresses. It is not recommended as the first line of management.
References
- Reynolds JD, Dobson V, Quine GC, Fielder AR, Palmer EA, Saunders RA, et al, for CRYO-ROP and LIGHT-ROP Cooperative Groups. Evidence based screening criteria for ROP. Natural history data from the CRYO-ROP and LIGHT-ROP studies. Arch Ophthalmol 2002;120:1470-76.
- The Committee for the classification of Retinopathy of Prematurity. An international classification for retinopathy of prematurity. Arch Ophthalmol. 1984;102:1130-1134.
- ICROP Committee for the classification of late stages of retinopathy of prematurity, II. The classification of retinal detachment. Arch Ophthalmol. 1987;105: 906-912.
- An international committee for the classification of retinopathy of prematurity. The international classification of retinopathy of prematurity revisited. Arch Ophthalmol. 2005;123:991-999.
- Cryotherapy for Retinopathy of Prematurity Cooperative Group. Multicenter trail of cryotherapy for retinopathy of prematurity. Preliminary results. Arch Ophthalmol. 1988; 106:471-479.
- Early Treatment of Retinopathy of Prematurity Cooperative Group. Revised indications for the treatment of retinopathy of prematurity. Arch Ophthalmol 2003;121: 1684-96
- Shah PK, Narendran V, Kalpana N, Tawansy KA. Anatomical and visual outcome of stages 4 and 5 retinopathy of prematurity. Eye 2009, 23:176-180
