Anatomical and visual outcomes in eyes undergoing surgery for Stage 5 retinopathy of prematurity (ROP) Functional and anatomical outcomes a ft er primary lens-sparing pars plana vitrectomy for Stage 4 retinopathy of prematurity

Background: While lens-sacri (cid:222) cing vitrectomy is the standard approach to manage Stage 5 retinopathy of prematurity (ROP), scleral buckling has been used to manage some cases of Stage 4. Lens-sparing vitrectomy was popularized by Maguire and Trese in selected cases of Stage 4 disease. Purpose: To assess the functional and visual outcomes a ft er primary lens-sparing pars plana vitrectomy for Stage 4 ROP. Materials and Methods: In a retrospective, interventional, consecutive case series, the records of 39 eyes of 31 patients presenting with Stage 4 retinal detachment secondary to ROP who underwent primary two or three-port lens-sparing vitrectomy from January 2000 to October 2006 were evaluated. The outcomes studied at the (cid:222) nal follow-up visit were the retinal status, lens and medial clarity and visual acuity . Favorable anatomical outcome was de (cid:222) ned as the retinal rea tt achment of the posterior pole at two months a ft er the surgery; and favorable functional outcome was de (cid:222) ned as a central, steady and maintained (cid:222) xation, with the child following light. Results: At mean follow-up of 15 months, 74% of the eyes had a favorable anatomical outcome with single procedure. The visual status was favorable in 63% . The lens remained clear in all the eyes at the last follow-up, and the media clarity was maintained in 87%. Intraoperative complications included vitreous hemorrhage, pre-retinal hemorrhage and retinal break formation. Conclusions: Lens-sparing vitrectomy helps to achieve a favorable anatomical and functional outcome in selected cases of Stage 4 ROP.

retinal detachment. In cases with tractional fold in the temporal periphery (anterior Zone 2), all the sclerotomies were made in the nasal half of the sclera, with the surgeon sitt ing on the side opposite to the eye being operated.
While making sclerotomies for LSV, unlike conventional adult vitreoretinal (VR) surgeries, the microvitreoretinal (MVR) blade was directed straight vertically downward and parallel to the visual axis. MVR blade was also used to cut and to create an opening in trans-vitreal membranes in the meridian of sclerotomy for smooth and traction-free entry of blunt instruments such as vitreous cutt er and endoilluminator. During the surgery the instruments were kept as vertical as possible and precaution was taken not to cross the midline, so as to avoid the lens touch. It was necessary to swap the instruments between two superior sclerotomies to complete the surgery.
All the surgeries were performed either using Accurus surgical system (Alcon Inc. Fort Worth TX USA) or Millennium microsurgical system (Bausch and Lomb Inc. Rochester NY USA). Visualization was accomplished with binocular indirect ophthalmo microscope (BIOM system, Oculus, Wetzlar, Germany) or pediatric Lander lens system.
The posterior hyaloid face was oft en att ached and an att empt was made to separate it over the disc and retina to the extent possible. As much relief of the pre-retinal traction as possible was achieved. Elevated bleeders were diathermised. The extent of the surgery varied widely depending upon the conÞ guration of the detachment and the extent and location of Þ brous proliferation. The sclerotomies were closed using 7-0 vicryl sutures. At conclusion of the surgery, ß uid-air exchange was not performed as a routine procedure. Postoperatively topical steroid and cycloplegic drops were used for a period of six weeks.
Postoperatively the operated eye was evaluated with a binocular indirect ophthalmoscope for medial clarity, status of retina and any recurrent Þ brosis. Ultrasonography was done periodically, to Þ nd out the retinal status if vitreous hemorrhage precluded fundus visualization. Repeat surgical intervention was done if required aft er three to four weeks.
Anatomical success was defined as total reattachment of the retina or at least posterior polar reatt achment. Visual status was evaluated based on the age at assessment-Þ xing and following behavior; with Leas symbols; or with Snellen's visual acuity chart. Intraocular pressure was measured with tono-pen, whenever possible.

Results
The demographics and surgical outcome of the study group are listed in Tables 1 and 2. Thirty-nine eyes of 31 patients that underwent primary LSV for Stage 4a or 4b ROP formed the subjects of this study. There were 20 male children (25 eyes) and 11 female children (14 eyes). Bilateral LSV was carried out in eight patients (26%). The mean birth weight was 1242 g (range 650-2250 g) and the mean gestational age at birth was 29 weeks (range 24 -34 weeks). The mean age at presentation to us was 37.6 weeks (range 32-52 weeks) and the mean age at the time of surgery was 42 weeks (range 36-57 weeks). Thirteen of the 31 babies were born aft er caesarian section while the rest were born aft er normal vaginal delivery.
Thirty-four eyes (87%) had undergone peripheral retinal ablation in the form of laser photocoagulation or cryopexy while Þ ve eyes presented to us with Stage 4a or b but without any prior treatment.
The status of fellow eye: Eight eyes underwent bilateral LSV. Fourteen out of the remaining 23 eyes had regressed ROP following laser photocoagulation; six eyes with Stage 4 (a or b) were not operated due to various reasons, while one eye had undergone scleral buckling elsewhere. Two eyes were in Stage 5 ROP.
Anterior segment examination revealed rubeosis in six eyes (15%) preoperatively, of which three eyes had pupils resistant to dilatation.
Preoperatively, intraocular hemorrhage was noted in 13 eyes (33%), preretinal hemorrhage in eight eyes; vitreous hemorrhage in three eyes and combined preretinal and vitreous hemorrhage in two eyes.
The location of tractional retinal detachment (TRD) in Stage 4a ROP was in the temporal quadrant in seven eyes (24%), superior and inferior to the disc in six eyes (21%) each, and nasal to the disc in Þ ve eyes (17%). Radiating peripapillary folds were seen in Þ ve eyes (17%) due to prepapillary traction. In eyes with Stage 4b, the location of TRD was mainly over the posterior pole, with nasal dragging of macula in two eyes, and TRD extending to the temporal periphery in one eye. This localization of TRD did not aff ect the anatomical or functional outcome, but was helpful in deciding the plan of surgery, including the placement of sclerotomies.
Intraoperatively, adequate relief of traction was achieved in 37 eyes (95%). While signiÞ cant intraoperative bleeding occurred in 13 (33%) eyes, only in two eyes, the bleeding was severe enough not to permit adequate dissection. Iatrogenic retinal breaks occurred in three eyes (8%), of which one developed total retinal detachment postoperatively, and underwent lensectomy and vitrectomy. The remaining two eyes underwent ß uid-gas exchange, endolaser and perß uoropropane (C 3 F 8 ) gas injection during the same sitt ing. All these three eyes att ained favorable anatomical results at the last follow-up.
The mean follow-up period was 15 months (range 2-55 months). One patient (Stage 4a) was lost to follow-up aft er the surgery. At the follow-up examination, 28 of 38 eyes (74%) achieved a complete or posterior pole retinal reatt achment with one procedure [Figures 1a and b]. These included 23 eyes (82%) with Stage 4a ROP and Þ ve eyes of Stage 4b ROP. Lens clarity was maintained in all eyes.
Of the 10 eyes (26%) with primary failures, seven underwent further surgery in the form of lensectomy and membrane dissection. In six of these, total or posterior pole reatt achment was achieved postoperatively.
The mean birth weight and gestational age of babies with primary success was 1187.4 g and 28.5 weeks respectively, as compared to 1395 g and 30 weeks in primary failure cases. All the 10 patients with primary failures had at least two systemic diseases, and eight had at least three or more systemic diseases at birth. In general, the eyes which had a primary failure following surgery were found to have a stormier prenatal and natal period, with more aggressive and advanced disease at presentation.   The visual outcomes followed the anatomical trends. Aft er one procedure, out of the 28 anatomically successful eyes, 24 had achieved good central, steady and maintained Þ xation. Out of these there were 20 eyes with Stage 4a and four with Stage 4b ROP. The Þ nal visual outcome was favorable in 30 of 38 eyes (79%). This constituted 24 of 28 Stage 4a ROP eyes (86%), and six of 10 Stage 4b ROP eyes.
Statistical analysis was performed using analytical soft ware SPSS Version 14.0 (Chicago, Illinois). Variables like birth weight, gestational age, age at presentation and stage of ROP at surgery were studied using binary logistic regression analysis. Factors like sex, location of TRD, preoperative pre-retinal hemorrhage, preoperative vitreous hemorrhage, and intraoperative complications were studied using Chi square test. None of the factors studied were found to be statistically signiÞ cant in terms of favorable anatomical or functional outcomes.

Discussion
The surgical management of Stage 5 ROP has been unsatisfactory. [1,10] Stage 4 ROP was earlier managed with scleral buckling, however, this procedure had certain limitations. It did not restore normal retinal anatomy and was unsuitable for cases with very posterior disease, though it was satisfactory for relieving peripheral traction. Although the lens is spared during scleral buckling procedure, anisometropia can still occur and be a cause of amblyopia. [11,12] Maguire et al., [3] introduced the concept of lens-sparing vitrectomy which was more capable of relieving the posterior traction (Zone 1 and posterior Zone 2 ROP) and restoring near normal anatomy. [12] In the present series, the initial few surgeries were performed with a two-port system, however, later we preferred a three-port system for lens-sparing vitrectomy in these eyes. It helped to maintain the intraocular pressure during the procedure and during the closure of other sclerotomies at the conclusion of surgery. Also, this system permits the surgeon to switch hands in order to perform anterior dissection without the risk of transient globe hypotony and lens touch. Previously, authors have shown a concern over the placement of the infusion cannula in the inferotemporal quadrant and rotating the eye into the same quadrant, which may cause lens injury either by a direct mechanical contact or by the hydrostatic forces from the infusion stream due to the small lid Þ ssure. [6] However, we did not Þ nd this signiÞ cant in our cases, as there was no lens injury and the lens remained clear in all the patients at the last follow-up visit, irrespective of whether two or three-port vitrectomy was performed.
This is one of the few studies providing the visual outcomes in addition to the anatomical outcomes and complications of LSV in Stage 4 ROP in the same paper. In the present series, the success has been good, with favorable anatomical outcome in 23 of the 28 eyes (82%) in Stage 4a and Þ ve out of 10 eyes in Stage 4b ROP with a single procedure. The visual results were favorable in eyes with successful retinal reatt achment. The Stage 4a ROP eyes att ained adequate vision in 71% (86% aft er second procedure) eyes. In Stage 4b, four out of 10 eyes had favorable functional outcome (six eyes aft er second procedure). It is evident that where the macula was involved in the detachment (Stage 4b), the results were less satisfactory, both anatomical and visual. Although the numbers were small to come to a deÞ nite conclusion, the diff erence in results points to the fact that anatomical results carry an implication on the functional results. The reported superior functional results aft er LSV for Stage 4a in the literature support our belief. [4,5,8] Although the success rate with only Stage 4a is comparable, overall success rate in our series is lower compare to a few published reports. [4,6,8] Compared to other reported series, mean gestational age, birth weight and mean age at surgery was higher in our series. These factors might be responsible for the relatively lower success in our series. Even in a subgroup of primary failure in our series itself, the mean birth weight and gestational age was higher compared to the rest of the infants in the series. Yu et al., [13] have also reported relatively lower success rate, 75.0% and 66.6%, in Stage 4a and 4b ROP respectively in their series with mean birth weight of 1224 g.
The pathoanatomy was found to be varied ranging from focal traction restricted to the ridge area to signiÞ cant proliferation extending from the optic disc. In most cases there was vitreous schisis, with sheets of vitreous still adherent to the posterior retina while there were membranes mimicking posterior vitreous detachment adherent to the ridge. An att empt was made to peel all vitreous remnants from the retina, at least up to the ridge. The extent of intraoperative hemorrhage was also variable and not always predictable from the preoperative picture. Where Þ brovascular tissue was trimmed, it could be cauterized but surface retinal ooze was left to stop on its own. Postoperatively some amount of vitreous hemorrhage was usually present but tended to clear in days to weeks. Re-surgery was done if the hemorrhage failed to clear in three to four weeks or if ultrasonography showed evidence of increasing TRD, instead of sett ling TRD.
In most cases the TRD settled rapidly and by six weeks postoperatively, the retina had near normal conÞ guration barring the photocoagulation marks. Where residual traction was present, the configuration of the retina was to that extent distorted, depending on the location of the fibrous tissue [ Figure 1b]. Surgical failure was due to re-proliferation leading to persistent or increasing TRD. In most of these cases, a lens sacriÞ ce was needed to adequately remove the Þ brosis in the second sitt ing.

Conclusions
Lens-sparing vitrectomy has a decisive role in the management of eyes with ROP that have progressed to Stage 4 despite adequate laser photocoagulation. The results of LSV for Stage 4a and 4b ROP are very satisfactory in our series, both in terms of anatomical success and functional outcome, although this procedure is associated with a few intra-and postoperative complications.