- Email: [email protected]
Advanced Retinopathy of Prematurity
Advanced Retinopathy of Prematurity The Anatomic and Visual Results of Vitreous Surgery JOHN D. ZILIS, MD,t EUGENE deJUAN, MD,2 ROBERT MACHEMER, MD2
Abstract: The anatomic and visual results of vitreous surgery in 140 eyes of 108 children with stage 4 and 5 retinopathy of prematurity (ROP) were reviewed. Macular attachment was achieved in 9 (64%) of 14 eyes with stage 4. In stage 5 eyes, partial posterior attachment was obtained in 38 (31%) of 121 eyes and complete posterior attachment was obtained in 11 eyes (9%). Final visual acuity of fix and follow or greater occurred in 6 (43%) of 14 eyes with stage 4 and in 13 eyes (11 %) with stage 5 ROP. Retinal detachment (RO) funnel configurations were classified according to the International Committee on ROP. The funnel type which was wide anteriorly and wide posteriorly had the best anatomic (63%) and visual (19%) success. Reoperation rarely improved visual acuity (4%), although reattachment was possible in 6 (22%) of 27 eyes. All children in this series underwent surgery by 2 years of age. Anatomic and visual success was achieved less often in children who underwent surgery at age 6 months or younger. Ophthalmology 1990; 97:821-826
Advanced retinopathy of prematurity (ROP) with retinal detachment (RD) remains a devastating problem. Although the recent ROP cryotherapy multicenter trial\,2 has shown the efficacy of peripheral retinal cryotherapy in high-risk eyes, a significant number of these eyes still progress to RD. We analyzed our results of vitreous surgery in eyes with stages 4 and 5 ROP.
Originally received: September 25, 1989. Revision accepted: January 15, 1990. 1
2
Devers Eye Institute, Portland. Duke University Eye Center, Durham.
Supported in part by National Eye Institute grant 1 F32 EY06046, the Helena Rubinstein Foundation, New York, and Research to Prevent Blind· ness, Inc., New York. Presented at the American Academy of Ophthalmology Annual Meeting, New Orleans, Oct/Nov 1989. Reprint requests to Eugene deJuan, MD, Duke University Eye Center, Durham, NC 27710.
PATIENTS AND METHODS A consecutive series of 140 eyes of 108 patients underwent vitreous surgery for ROP stage 4, partial RD, or stage 5, total RD, between 1978 and 1988 and were evaluated retrospectively. All patients were 2 years of age or younger at the time of surgery and were followed for at least 6 months postoperatively. Forty-six of these patients were included in a preliminary report. 3 Five patients had less than 6 months follow-up and were excluded from this study. The average birth weight was 955 g (range, 560-1850 g). The mean gestational age was 26.3 weeks (range, 2232 weeks). The average age at the time of surgery was 8.6 months (range, 3-24 months). Preoperatively and at postoperative visits, children underwent clinical assessment which included ocular and medical history, visual acuity testing, intraocular pressure (lOP) measurements (by pneumotonometry or Schi0tz tonometry), and ocular 821
OPHTHALMOLOGY
•
JUNE 1990
Table 1. Final Anatomic Outcome No. of Eyes
(%)
Stage 4 9 4 1
(64) (29) (7)
14
(100)
11 38 58 14
(9) (31) (48) (12)
121
(100)
Macular attachment Total detachment Uncertain Total Stage 5 Total attachment Partial attachment Total detachment Uncertain Total
Table 2. Final Visual Acuity Results Stage 4 Visual Acuity Fixation and following Light perception No light perception Uncertain Total
No. of Eyes
Stage 5 (%)
No. of Eyes
(%)
6 5 3
(43) (36) (21)
13 68 30 10
(11 ) (56) (25) (8)
14
(100)
121
(100)
examination with indirect ophthalmoscopy and ultrasonography. At the time of surgery, examination under anesthesia included measurements of corneal diameter and lOP, slit-lamp biomicroscopy, dilated indirect ophthalmoscopy with scleral depression, ultrasonography, and fundus photography. Patients underwent surgery which included vitrectomy, lentectomy, and removal of proliferative membranes. 3,4 On occasion, scleral buckling with gas tamponade and external subretinal fluid drainage was done when a retinal tear or Schlieren were noted during surgery. Schlieren are optical phenomenon occurring when two clear fluids of different optical densities mix. 5 The presence of these streaks is often associated with the escape of subretinal fluid into the vitreous space via a retinal hole. Preoperative RD configurations were classified using indirect ophthalmoscopy and ultrasonography. According to International Retinopathy of Prematurity committee criteria,6 categories included partial RD not involving the macula, stage 4a (1 eye); partial RD involving the macula, stage 4b (13 eyes); and total RD, stage 5, (121 eyes). In 92 eyes with stage 5 RD, subclassification according to funnel configuration was done. The anterior and posterior areas of the funnel were assessed as wide (open) or narrow (closed). Thirty eyes were classified as wide/wide, 24 eyes as wide/narrow, 2 eyes as narrow/wide, and 36 eyes as narrow/narrow. 822
•
VOLUME 97
•
NUMBER 6
At presentation, all cases had bilateral advanced disease of at least severe stage 3 in the fellow eye. Vitreous surgery was not recommended when the fellow eye was normal or in eyes with obvious buphthalmos and documented glaucoma. Visual acuity was assessed by the vitreoretinal fellow, resident, or ophthalmic technician and was confirmed by the attending physician. Unfortunately, on occasion, children were sedated before examination by the physician which precluded an accurate assessment of vision. These eyes were excluded from the analysis of visual acuity changes after surgery. Visual acuity was assessed monocularly. A penlight or small, bright test object was used to assess purposeful visual behavior such as fixation and following or reaching for objects. Such a positive and reproducible response was classified as fixation and following. If such a response was lacking, then the indirect ophthalmoscope was used to elicit an avoidance response such as a blink. When this type of response was present and reproducible, the child's visual acuity was recorded as light perception. A child was considered to have probable light perception if the response elicited was inconsistent but present. In such cases, a positive history of some visual behavior obtained from the parents was also required. For purposes of analysis, the probable light perception and light perception visual acuities were grouped together. If a child did not respond to repeated examination with bright light or movement and there was no history of visual behavior, the visual acuity was recorded as no light perception. Final postoperative visual acuity was determined using the child's most recent examination. All patients had at least 6 months offollow-up, and 95 of 135 eyes had additional later visits. The overall mean follow-up in this series was 22.4 months. Data were analyzed statistically using Fisher's exact test.
RESULTS STAGE 4
Vitreous surgery was done for partial RD (stage 4) in 14 eyes of children 2 years of age or younger. The detachment involved the macula in 13 eyes (stage 4b), and the macula was threatened in one eye (stage 4a). Macular attachment was achieved in nine eyes. Four eyes became completely detached. One eye had posterior partial attachment, but macular attachment was uncertain (Table 1). Final postoperative visual acuity was fixation and following or greater in six eyes (43%), light perception in five eyes (36%), and no light perception in three eyes (21 %) (Table 2). When compared with preoperative visual acuity, five eyes (36%) improved to fixation and following vision or better postoperatively. Two eyes (14%) declined, both to no light perception (Fig 1). STAGE 5
Anatomic success, defined as at least partial posterior retinal attachment, was achieved in 49 (40%) of 121 eyes
ZILIS et al
•
VITREOUS SURGERY FOR ADVANCED ROP
40
100 90 80 70 (fl
OJ
>,
w
'0
'*"
60
_
- Total Eyes
~
- Visual Improvement (Fix and Follow) Visual Decrease (No Light Perception)
35
_
- Attached
~
- Detached
30
o -
(fl
OJ
>,
w
50
4-
0
40
"*
30 20
25 20 15 10 5
10 0 Stage 4
Fig 1. Visual acuity outcome after vitreous surgery for stages 4 and 5 retinopathy of prematurity. Patients without visual acuity change are not plotted.
of89 patients with stage 5 ROP (Table 1). Eleven of these eyes were completely attached posteriorly. Fifty-eight eyes (48%) remained completely detached. Final retinal configuration was uncertain in 14 eyes (12%), usually because B-scan ultrasonography was not available. Final postoperative visual acuity of fixation and following or better was recorded in 13 (11 %) of 121 eyes. Light perception was noted in 68 eyes (56%). No light perception was found in 30 eyes (25%). In ten eyes (8%), final visual acuity could not be determined or was not recorded (Table 2). Of 101 eyes in which both pre- and postoperative visual acuity was recorded and compared, 12 (12%) improved to the level of fixation and following (Fig 1). This level of visual acuity, once achieved, showed no evidence of decline over subsequent postoperative visits in all 12 eyes, although six eyes required greater than 6 months of postoperative follow-up before such acuity was evident. Four eyes with preoperative recorded vision of no light perception had light perception vision postoperatively. Twentysix eyes (26%) had decreased visual acuity postoperatively, all to the level of no light perception. Seventeen of these eyes showed no light perception 6 months after surgery with an additional nine eyes declining over a longer followup period. In 92 eyes, the preoperative RD had been characterized according to funnel configuration. Figure 2 displays the anatomic successes (at least partial posterior attachment) and anatomic failures (complete detachment) of stage 5 by category. Anatomic success by category was: wide/wide, 19 (63%) of 30 eyes; wide/narrow, 10 (42%) of 24 eyes; narrow/wide, 1 (50%) of2 eyes (50%); and narrow/narrow, 11 (31%) of36 eyes. Visual outcome for the various preoperative RD configurations is shown in Figure 3. Improvement to fixation and following vision in the category wide/wide occurred in 5 (19%) of 27 eyes. In the wide/narrow group of 22 eyes, 1 (5%) improved to fix and follow. Visual improvement did not occur in the two eyes with narrow/wide configuration. The narrow/narrow category showed postoperative visual improvement to fix and follow in only 3 (9%) of 35 eyes.
-
0
Stage 5
wide/wide
wide/narrow
-"""
narrow/wide
narrow/narrow
Preoperative Retinal Configuration of Stage 5 ROP
Fig 2. Anatomic outcome of surgery for stage 5 retinopathy of prematurity, grouped according to preoperative retinal funnel configuration. 40 35 30 (fl (J)
>,
w
4-
0
"*
_
- Total Eyes
M
- Visual Improvement
o -
(Fix and Follow)
Visual Decrease
(No Light Perception)
25 20 15 10 5
0 wide/wide
wide/narrow
narrow/wide
narrow/narrow
Preoperative Retinal Configuration of Stage 5 ROP
Fig 3. Visual outcome of vitreous surgery for various stage 5 retinopathies of prematurity, grouped according to preoperative retinal funnel configuration. Patients without visual acuity change are not plotted.
Visual acuity decline to no light perception in category wide/wide was found in four eyes (16%). The wide/narrow group of 22 eyes showed such visual decline in 8 eyes (36%). One of two eyes with narrow/wide configuration had no light perception as did 10 (29%) of 35 eyes. The postoperative retinal configuration and the final vision were determined in 107 stage 5 eyes (Table 3). For all cases, postoperative retinal attachment, partial or complete, was more likely to be associated with fixation and following vision than was the completely detached retinal configuration (P = 0.01). A final visual acuity of no light perception was more commonly found with total RD than with the partial or complete attachment (P = 0.03). Analysis of the individual preoperative detachment configuration categories (i.e., wide/wide) compared in such a manner did not show significant differences. When visually successful cases with final visual improvement to at least fix and follow (n = 12) were analyzed and compared with visual failure cases in which the final visual acuity decrease was no light perception (n = 26), no significant differences in surgical technique or com823
OPHTHALMOLOGY
•
JUNE 1990
•
VOLUME 97
Preoperative Retinal Configuration Stage 5
Postoperative Configuration Attached (n = 49) Detached (n = 58)
Failure (no light perception)
No. of Eyes (%)
No. of Eyes (%)
10 (20)* 2 (3)
6 (12) 20 (34)t
NUMBER 6
45
Table 3. Postoperative Retinal Configuration versus Visual Outcome Visual Success (fix and follow)
•
40 35 Vl
Q)
_
- Total Eyes
~
- Anatomic Success
30
>.
w
25
'0
20
'#:
15 10
p= 0.01 . t P= 0.03. *
5 0
Table 4. Stage 5 Eyes Final Visual Acuity No. of eyes Preoperative elevated intraocular pressure Postoperative elevated intraocular pressure Hypotony Intraoperative break Schlieren Peripheral trough dissection
No Light Perception (no. of eyes)
12
26
2
2
1
1
2
7
13-18
7-12
19-24
Age (Months)
Fix and Follow (no. of eyes)
o
0-6
Fig 4. Postoperative anatomic success as a function of the child's age at time of surgery. 45 40
3
1
2
5
10
35 Vl
Q)
25
0
20
'#:
15
- Total Eyes - Visual Improvement (Fix and Follow) Visual Decrease (No Light Perception)
o -
30
>.
w
_ ~
10
plications could be determined. Pre- and postoperative factors and operative complications are examined in Table 4 for those eyes in which vision improved to fix and follow or declined to no light perception. Preoperative lOP was elevated in 2 (8%) of 12 eyes in the visual improvement group and in 2 (8%) of 26 eyes in the visual failure group. Postoperative lOP elevation requiring treatment occurred in 1 (8%) of 12 eyes which visually improved and in 3 (11 %) of 26 eyes that declined to no light perception. Hypotony was recorded in one eye with no light perception. Massive bleeding, which could not be controlled, infection, and complications of anesthesia were not encountered in either group. Intraoperative peripheral retinal breaks were reported in 1 (8%) of 12 eyes with visual improvement and in 2 (8%) of 26 eyes with no light perception. All eyes with known breaks remained detached postoperatively. Schlieren, the streaks seen when two clear fluids of different optical densities mix, were noted without an observable retinal break in two eyes (17%) in the improved group and in five eyes (20%) in the no light perception group. Dissection of the peripheral retinal trough 7 was possible in 7 (58%) of 12 eyes in the visually successful category and in 10 (39%) of 26 eyes with no light perception (P = 0.346). The child's age at the time of vitreous surgery was considered and compared with anatomic success in Figure 4. Forty-five (42%) of the 107 eyes in which the final postoperative retinal configuration could be determined had vitreous surgery by 6 months of age. In this group, anatomic success was obtained in 12 eyes (27%). Anatomic 824
5 0
0-6
7-12
13-18
19-24
Age (Months)
Fig S. Visual outcome as a function of the child's age at the time of surgery. Patients without visual acuity change are not plotted.
success in the 62 eyes of children older than 6 months was achieved in 38 eyes (61 %). Figure 5 compares the child's age at surgery to visual outcome for those 101 eyes in which preoperative and final postoperative visual acuity were accurately obtained. In children who had surgery by 6 months of age (n = 38), one eye (3%) improved to fix and follow vision. In children older than 6 months of age at the time of surgery (n = 63), vision improved in 11 eyes (17%) to the level of fix and follow. In children who underwent surgery by age 6 months or younger, vision decreased to no light perception in 13 (34%) of 38 eyes. No light perception was the final visual outcome in 13 (21 %) of 63 eyes in those children operated on at ages greater than 6 months of age (P = 0.177). The percentage of eyes with improved visual acuity (fixation and following) as a function of retinal attachment (anatomic success) was determined for the two age groups. For children 6 months of age or younger, 1 (8%) of 12 eyes with known attached retinas had improved vision, and in children over 6 months of age, 11 (29%) of 38 eyes with anatomic success also had improved visual acuity. Plus disease, defined as abnormal dilation and tor-
ZILIS et al
•
VITREOUS SURGERY FOR ADVANCED ROP
tuosity of retinal vessels,l was identified in eight eyes preoperatively. All cases occurred in children younger than 6 months of age at the time of surgery. Partial retinal attachment was possible in two eyes (25%). Improved vision did not occur postoperatively, and two eyes had no light perception. Twenty-seven eyes in the stage 5 group underwent a reoperation involving additional vitreous surgery. In 17 eyes with total RD, reoperation resulted in at least partial posterior attachment in five eyes. In ten eyes with partial attachment before reoperation, only one eye gained complete posterior attachment, although often with reoperation, further release of traction with retinal unfolding was achieved. Overall, vision improved in only one patient (4%) and decreased in four (15%).
DISCUSSION Vitreous surgery for RD in advanced ROP continues to evolve. 3,7-9 For example, we have learned that a more anterior approach, 7 entering the eye in front of the iris combined with lentectomy, results in fewer tears in the anteriorly detached retina and pars plana epithelium. Our efforts in these small eyes have been aided greatly with the modification and new design of surgical instrumentation. With the knowledge that the adequate release of traction is of paramount importance in these eyes, we have become more aggressive in our attempts to remove proliferations, particularly in the region of the peripheral trough. 7 However, this approach to membrane removal is tempered by the knowledge that retinal breaks in these eyes can be a devastating complication. In this report, we analyzed the anatomic and visual results of our surgical approach to stages 4 and 5 ROP over the past 10 years. Trese8 in 1984 reported that 18 (40%) of 40 eyes with stage 5 ROP were attached 6 months after surgery and that closed funnels had only a 26% anatomic reattachment rate. In 1986, we reported4 a 43% rate of anatomic success in 58 eyes of children with combined stages 4 and 5 ROP operated on by 1 year of age. Our current, larger series of 135 children showed an anatomic success of 40% (49 of 121 eyes) with stage 5 ROP compared with our previous 1986 report in which 33% (15 of 46 eyes) with stage 5 ROP were surgically reattached. With increasing surgical sophistication, more difficult cases have been attempted. As an example, in this series, the narrow/narrow preoperative funnel configuration6 represents 40% (36 of 92 eyes) of stage 5 eyes compared with only 16% (7 of 45 eyes) in 1986. As expected,3,8 in this current series, the wide/wide funnel configuration had the best attachment rate, 63% (19 of30 eyes), and the narrow/narrow category had the poorest, 31 % (11 of 36 eyes). Anatomic success as a function of a child's age at the time of vitreous surgery showed that only 27% (12 of 45 eyes) of infants 6 months of age or younger were successfully attached compared with 61 % (38 of 62 eyes) of those older than 6 months at the time of surgery. We can speculate that in this nonrandomized, retrospective anal-
ysis, there may be a bias in the selection process of children of different ages. Older ages may represent more favorable cases since eyes which were already blind or had glaucoma were not selected for surgery. Further, the clinical activity of the disease and the risk of reproliferation may be greater in younger children. 9 In this report, all of the eight eyes of children with plus disease were younger than 6 months at the time of surgery. Despite better anatomic results, only a small percentage of children have significant postoperative visual improvement. Unfortunately, in these infants, the accuracy of visual acuity testing is limited. Even full-term infants with presumed normal visual and neurologic development tested with Teller preferentiallooking iO seldom attain reproducible 6/60 levels of visual acuity until 4 months of age. II Therefore, it is not surprising that visual acuity testing in premature infants with variable degrees of neurologic delay and severe retinopathy will yield low and sometimes inconsistent results. U sing the broad categories of: (1) purposeful, fixation, and following vision; (2) primitive, light perception; and (3) no light perception, we found that improved postoperative vision to the level of fixation and following occurred in 35% (5 of 14 eyes) with stage 4 ROP and in only 12% (12 of 101 eyes) with stage 5 ROP compared with preoperative vision (Fig 1). Vision decreased to no light perception postoperatively in 2 (14%) of 14 eyes with stage 4 and in 26 (26%) of 101 eyes with stage 5 ROP (Fig 1). Of special interest were those six eyes in which surgery was performed when no consistent light perception could be demonstrated preoperatively. Four ofthese eyes showed improvement to light perception, and two remained with no light perception. This highlights our problems with the accurate assessment of low vision in these infants. Retinal attachment in stage 5 eyes was significantly more likely to result in improved visual acuity (P = 0.01). Conversely, continued postoperative RD was likely to result in no light perception (P = 0.03) (Table 3). Visual improvement in stage 5 eyes occurred most frequently in the wide/wide funnel configuration with 17% attaining fixation and following acuity. Factors such as lOP, hypotony, and surgical complications in the visually improved (fix and follow) category were compared with the visual failure category (Table 4). No significant differences were found, although the numbers of patients are small. In autopsy eyes of children with stage 5 ROP, severe photoreceptor inner segment loss and retroretinal membrane formation has often been observed l2 ,13 which was inapparent clinically. These chronic changes may account, in part, for the many eyes which were attached successfully without improvement in postoperative visual acuity, Therefore, earlier surgical intervention after RD should enhance visual results. Evidence in the pediatric literature ll suggests that in cases of bilateral congenital cataracts, surgical intervention before 8 weeks of life increases the chances of visual rehabilitation. Wiesel and Hubel 14 showed that irreversible amblyopia with loss of geniculocortical neurons occurs 825
OPHTHALMOLOGY
•
JUNE 1990
in kittens occluded for the first 8 and 12 weeks of life, respectively. However, the damage induced by occlusion for shorter periods of time may be reversible. Furthermore, is the potential for vision dependent on a certain period of retinal attachment before detachment occurs? Why then did children in this study show less postoperative visual acuity improvement if their surgery was performed at 6 months of age or younger (1 of 38 eyes or 3%) than if they were operated on after 6 months of age (11 of 63 eyes or 16%)? Because fewer eyes were reattached in the younger age group, those cases with visual improvement as a function of retinal reattachment for each group was determined. Only 8% of attached retinas in the younger group had improved postoperative visual acuity compared with 29% of the older group (P = 0.02). The reasons for such results remain unknown. This observation may be biased because of the relatively small numbers of patients and arbitrary selection process in this retrospective series, but we also may speculate that other factors might playa role. Is the regenerative capacity of the retina dependent on a certain level of development? Do detachments that occur before adequate macular developmene s,16 result in more profound amblyopia? Flynn 1? noted that if the conceptual age of these premature infants is calculated, these children are actually months younger than full-term infants at the time of examination. For example, a child with a gestation of only 26 weeks who undergoes surgery at 4 months of age has a conceptual age of only 42 weeks at the time of surgery. At that age, macular development may be incomplete 1S ,16 and perhaps may contribute to the poor functional results obtained. Although it was our observation that reoperation involving additional vitreous surgery usually provided additional release of traction with further unfolding of the retina, posterior reattachment occurred in only 22% (6 of 27 eyes), and vision improved in only one eye (4%). We therefore have become more reluctant to recommend reoperations. Vitreous surgery for advanced ROP, particularly stage 5, has led to increases in the number and type of anatomic successes, yet visual improvement remains extremely low, both in percentage and level of improvement for all categories of stage 5 ROP. Although our data showed that the anatomic and especially the visual outcome of surgery in children younger than 6 months of age was poorer than in older children, visual results in all ages are too low. Therefore, we have not abandoned the concept of early intervention but instead argue that fundamental changes in our approach are necessary if the prognosis is to improve. Thanks largely to the Cryo-ROP trial,l enhanced surveillance of high-risk infants with appropriate intervention at the threshold level should decrease the numbers of chil- .
826
•
VOLUME 97
•
NUMBER 6
dren who advance to RD. In those children who do develop partial RD despite cryotherapy, scleral buckling may be beneficial, and a clinical trial is being considered. In addition, cryotherapy appears to lessen the vascular activity (plus) of the disease. Therefore, early vitreous surgery in infants who have been previously treated with cryotherapy before their RD may lead to greater successes in the future.
REFERENCES 1. Cryotherapy for Retinopathy of Prematurity Cooperative Group. MUlticenter trial of cryotherapy for retinopathy of prematurity: preliminary results. Arch Ophthalmol1988; 106:471-9. 2. Tasman W. Multicenter trial for cryotherapy for retinopathy of prematurity [Editorial]. Arch Ophthalmol1988; 106:463-4. 3. Machemer R. Closed vitrectomy for severe retrolental fibroplasia in an infant. Ophthalmology 1983; 90:436-41. 4. Chong LP, Machemer R, deJuan E. Vitrectomy for advanced stages of retinopathy of prematurity. Am J Ophthalmol1986; 102:710-6. 5. Friberg TR, Tano Y, Machemer R. Streaks (Schlieren) as a sign of rhegmatogenous detachment in vitreous surgery. Am J Ophthalmol 1979; 88:943-4. 6. The International Committee for the Classification of the Late Stages of Retinopathy of Prematurity. An international classification of retinopathy of prematurity: II. The classification of retinal detachment. Arch Ophthalmol1987; 105:906-12. 7. deJuan E Jr, Machemer R. Retinopathy of prematurity: surgical technique. Retina 1987; 7:63-9. 8. Trese MT. Surgical results of stage V retrolental fibroplasia and timing of surgical repair. Ophthalmology 1984; 91 :461-6. 9. Charles S. Vitreoretinal surgery for retinopathy of prematurity. In: Flynn JT, Phelps DL, eds. Retinopathy of Prematurity: Problem and Challenge. New York: Alan R. Liss, 1988; 287-93. (Birth defects original article series; v. 24, no. 1) 10. Teller DY, Morse R, Borton R, Regal D. Visual acuity for vertical and diagonal gratings in human infants. Vision Res 1974; 14:1433-9. 11. Rogers GL, Tishler CL, Tsou BH, et al. Visual acuities in infants with congenital cataracts operated on prior to 6 months of age. Arch Ophthalmol 1981; 99:999-1003. 12. Foos RY. Retinopathy of prematurity: pathologiC correlation of clinical stages. Retina 1987; 7:260-76. 13. deJuan E Jr, Machemer R, Flynn JT, Green WR. Surgical pathoanatomy in stage 5 retinopathy of prematurity. In: Flynn JT, Phelps DL, eds. Retinopathy of Prematurity: Problem and Challenge. New York: Alan R. Liss, 1988; 281-6. (Birth defects original article series; v. 24, no. 1) 14. Wiesel TN, Hubel DH. Comparison of the effects of unilateral and bilateral eye closure on cortical unit responses in kittens. J Neurophysiol 1965; 28:1029-40. 15. Isenberg SJ. Macular development in the premature infant. Am J Ophthalmol1986; 101 :74-80. 16. Hendrickson AE, Yuodelis C. The morphological development of the human fovea. Ophthalmology 1984; 91 :603-12. 17. Flynn JT. Acute proliferative retrolental fibroplasia: multivariate risk analysis. Trans Am Ophthalmol Soc 1983; 81 :549-91.
Abstract: The anatomic and visual results of vitreous surgery in 140 eyes of 108 children with stage 4 and 5 retinopathy of prematurity (ROP) were reviewed. Macular attachment was achieved in 9 (64%) of 14 eyes with stage 4. In stage 5 eyes, partial posterior attachment was obtained in 38 (31%) of 121 eyes and complete posterior attachment was obtained in 11 eyes (9%). Final visual acuity of fix and follow or greater occurred in 6 (43%) of 14 eyes with stage 4 and in 13 eyes (11 %) with stage 5 ROP. Retinal detachment (RO) funnel configurations were classified according to the International Committee on ROP. The funnel type which was wide anteriorly and wide posteriorly had the best anatomic (63%) and visual (19%) success. Reoperation rarely improved visual acuity (4%), although reattachment was possible in 6 (22%) of 27 eyes. All children in this series underwent surgery by 2 years of age. Anatomic and visual success was achieved less often in children who underwent surgery at age 6 months or younger. Ophthalmology 1990; 97:821-826
Advanced retinopathy of prematurity (ROP) with retinal detachment (RD) remains a devastating problem. Although the recent ROP cryotherapy multicenter trial\,2 has shown the efficacy of peripheral retinal cryotherapy in high-risk eyes, a significant number of these eyes still progress to RD. We analyzed our results of vitreous surgery in eyes with stages 4 and 5 ROP.
Originally received: September 25, 1989. Revision accepted: January 15, 1990. 1
2
Devers Eye Institute, Portland. Duke University Eye Center, Durham.
Supported in part by National Eye Institute grant 1 F32 EY06046, the Helena Rubinstein Foundation, New York, and Research to Prevent Blind· ness, Inc., New York. Presented at the American Academy of Ophthalmology Annual Meeting, New Orleans, Oct/Nov 1989. Reprint requests to Eugene deJuan, MD, Duke University Eye Center, Durham, NC 27710.
PATIENTS AND METHODS A consecutive series of 140 eyes of 108 patients underwent vitreous surgery for ROP stage 4, partial RD, or stage 5, total RD, between 1978 and 1988 and were evaluated retrospectively. All patients were 2 years of age or younger at the time of surgery and were followed for at least 6 months postoperatively. Forty-six of these patients were included in a preliminary report. 3 Five patients had less than 6 months follow-up and were excluded from this study. The average birth weight was 955 g (range, 560-1850 g). The mean gestational age was 26.3 weeks (range, 2232 weeks). The average age at the time of surgery was 8.6 months (range, 3-24 months). Preoperatively and at postoperative visits, children underwent clinical assessment which included ocular and medical history, visual acuity testing, intraocular pressure (lOP) measurements (by pneumotonometry or Schi0tz tonometry), and ocular 821
OPHTHALMOLOGY
•
JUNE 1990
Table 1. Final Anatomic Outcome No. of Eyes
(%)
Stage 4 9 4 1
(64) (29) (7)
14
(100)
11 38 58 14
(9) (31) (48) (12)
121
(100)
Macular attachment Total detachment Uncertain Total Stage 5 Total attachment Partial attachment Total detachment Uncertain Total
Table 2. Final Visual Acuity Results Stage 4 Visual Acuity Fixation and following Light perception No light perception Uncertain Total
No. of Eyes
Stage 5 (%)
No. of Eyes
(%)
6 5 3
(43) (36) (21)
13 68 30 10
(11 ) (56) (25) (8)
14
(100)
121
(100)
examination with indirect ophthalmoscopy and ultrasonography. At the time of surgery, examination under anesthesia included measurements of corneal diameter and lOP, slit-lamp biomicroscopy, dilated indirect ophthalmoscopy with scleral depression, ultrasonography, and fundus photography. Patients underwent surgery which included vitrectomy, lentectomy, and removal of proliferative membranes. 3,4 On occasion, scleral buckling with gas tamponade and external subretinal fluid drainage was done when a retinal tear or Schlieren were noted during surgery. Schlieren are optical phenomenon occurring when two clear fluids of different optical densities mix. 5 The presence of these streaks is often associated with the escape of subretinal fluid into the vitreous space via a retinal hole. Preoperative RD configurations were classified using indirect ophthalmoscopy and ultrasonography. According to International Retinopathy of Prematurity committee criteria,6 categories included partial RD not involving the macula, stage 4a (1 eye); partial RD involving the macula, stage 4b (13 eyes); and total RD, stage 5, (121 eyes). In 92 eyes with stage 5 RD, subclassification according to funnel configuration was done. The anterior and posterior areas of the funnel were assessed as wide (open) or narrow (closed). Thirty eyes were classified as wide/wide, 24 eyes as wide/narrow, 2 eyes as narrow/wide, and 36 eyes as narrow/narrow. 822
•
VOLUME 97
•
NUMBER 6
At presentation, all cases had bilateral advanced disease of at least severe stage 3 in the fellow eye. Vitreous surgery was not recommended when the fellow eye was normal or in eyes with obvious buphthalmos and documented glaucoma. Visual acuity was assessed by the vitreoretinal fellow, resident, or ophthalmic technician and was confirmed by the attending physician. Unfortunately, on occasion, children were sedated before examination by the physician which precluded an accurate assessment of vision. These eyes were excluded from the analysis of visual acuity changes after surgery. Visual acuity was assessed monocularly. A penlight or small, bright test object was used to assess purposeful visual behavior such as fixation and following or reaching for objects. Such a positive and reproducible response was classified as fixation and following. If such a response was lacking, then the indirect ophthalmoscope was used to elicit an avoidance response such as a blink. When this type of response was present and reproducible, the child's visual acuity was recorded as light perception. A child was considered to have probable light perception if the response elicited was inconsistent but present. In such cases, a positive history of some visual behavior obtained from the parents was also required. For purposes of analysis, the probable light perception and light perception visual acuities were grouped together. If a child did not respond to repeated examination with bright light or movement and there was no history of visual behavior, the visual acuity was recorded as no light perception. Final postoperative visual acuity was determined using the child's most recent examination. All patients had at least 6 months offollow-up, and 95 of 135 eyes had additional later visits. The overall mean follow-up in this series was 22.4 months. Data were analyzed statistically using Fisher's exact test.
RESULTS STAGE 4
Vitreous surgery was done for partial RD (stage 4) in 14 eyes of children 2 years of age or younger. The detachment involved the macula in 13 eyes (stage 4b), and the macula was threatened in one eye (stage 4a). Macular attachment was achieved in nine eyes. Four eyes became completely detached. One eye had posterior partial attachment, but macular attachment was uncertain (Table 1). Final postoperative visual acuity was fixation and following or greater in six eyes (43%), light perception in five eyes (36%), and no light perception in three eyes (21 %) (Table 2). When compared with preoperative visual acuity, five eyes (36%) improved to fixation and following vision or better postoperatively. Two eyes (14%) declined, both to no light perception (Fig 1). STAGE 5
Anatomic success, defined as at least partial posterior retinal attachment, was achieved in 49 (40%) of 121 eyes
ZILIS et al
•
VITREOUS SURGERY FOR ADVANCED ROP
40
100 90 80 70 (fl
OJ
>,
w
'0
'*"
60
_
- Total Eyes
~
- Visual Improvement (Fix and Follow) Visual Decrease (No Light Perception)
35
_
- Attached
~
- Detached
30
o -
(fl
OJ
>,
w
50
4-
0
40
"*
30 20
25 20 15 10 5
10 0 Stage 4
Fig 1. Visual acuity outcome after vitreous surgery for stages 4 and 5 retinopathy of prematurity. Patients without visual acuity change are not plotted.
of89 patients with stage 5 ROP (Table 1). Eleven of these eyes were completely attached posteriorly. Fifty-eight eyes (48%) remained completely detached. Final retinal configuration was uncertain in 14 eyes (12%), usually because B-scan ultrasonography was not available. Final postoperative visual acuity of fixation and following or better was recorded in 13 (11 %) of 121 eyes. Light perception was noted in 68 eyes (56%). No light perception was found in 30 eyes (25%). In ten eyes (8%), final visual acuity could not be determined or was not recorded (Table 2). Of 101 eyes in which both pre- and postoperative visual acuity was recorded and compared, 12 (12%) improved to the level of fixation and following (Fig 1). This level of visual acuity, once achieved, showed no evidence of decline over subsequent postoperative visits in all 12 eyes, although six eyes required greater than 6 months of postoperative follow-up before such acuity was evident. Four eyes with preoperative recorded vision of no light perception had light perception vision postoperatively. Twentysix eyes (26%) had decreased visual acuity postoperatively, all to the level of no light perception. Seventeen of these eyes showed no light perception 6 months after surgery with an additional nine eyes declining over a longer followup period. In 92 eyes, the preoperative RD had been characterized according to funnel configuration. Figure 2 displays the anatomic successes (at least partial posterior attachment) and anatomic failures (complete detachment) of stage 5 by category. Anatomic success by category was: wide/wide, 19 (63%) of 30 eyes; wide/narrow, 10 (42%) of 24 eyes; narrow/wide, 1 (50%) of2 eyes (50%); and narrow/narrow, 11 (31%) of36 eyes. Visual outcome for the various preoperative RD configurations is shown in Figure 3. Improvement to fixation and following vision in the category wide/wide occurred in 5 (19%) of 27 eyes. In the wide/narrow group of 22 eyes, 1 (5%) improved to fix and follow. Visual improvement did not occur in the two eyes with narrow/wide configuration. The narrow/narrow category showed postoperative visual improvement to fix and follow in only 3 (9%) of 35 eyes.
-
0
Stage 5
wide/wide
wide/narrow
-"""
narrow/wide
narrow/narrow
Preoperative Retinal Configuration of Stage 5 ROP
Fig 2. Anatomic outcome of surgery for stage 5 retinopathy of prematurity, grouped according to preoperative retinal funnel configuration. 40 35 30 (fl (J)
>,
w
4-
0
"*
_
- Total Eyes
M
- Visual Improvement
o -
(Fix and Follow)
Visual Decrease
(No Light Perception)
25 20 15 10 5
0 wide/wide
wide/narrow
narrow/wide
narrow/narrow
Preoperative Retinal Configuration of Stage 5 ROP
Fig 3. Visual outcome of vitreous surgery for various stage 5 retinopathies of prematurity, grouped according to preoperative retinal funnel configuration. Patients without visual acuity change are not plotted.
Visual acuity decline to no light perception in category wide/wide was found in four eyes (16%). The wide/narrow group of 22 eyes showed such visual decline in 8 eyes (36%). One of two eyes with narrow/wide configuration had no light perception as did 10 (29%) of 35 eyes. The postoperative retinal configuration and the final vision were determined in 107 stage 5 eyes (Table 3). For all cases, postoperative retinal attachment, partial or complete, was more likely to be associated with fixation and following vision than was the completely detached retinal configuration (P = 0.01). A final visual acuity of no light perception was more commonly found with total RD than with the partial or complete attachment (P = 0.03). Analysis of the individual preoperative detachment configuration categories (i.e., wide/wide) compared in such a manner did not show significant differences. When visually successful cases with final visual improvement to at least fix and follow (n = 12) were analyzed and compared with visual failure cases in which the final visual acuity decrease was no light perception (n = 26), no significant differences in surgical technique or com823
OPHTHALMOLOGY
•
JUNE 1990
•
VOLUME 97
Preoperative Retinal Configuration Stage 5
Postoperative Configuration Attached (n = 49) Detached (n = 58)
Failure (no light perception)
No. of Eyes (%)
No. of Eyes (%)
10 (20)* 2 (3)
6 (12) 20 (34)t
NUMBER 6
45
Table 3. Postoperative Retinal Configuration versus Visual Outcome Visual Success (fix and follow)
•
40 35 Vl
Q)
_
- Total Eyes
~
- Anatomic Success
30
>.
w
25
'0
20
'#:
15 10
p= 0.01 . t P= 0.03. *
5 0
Table 4. Stage 5 Eyes Final Visual Acuity No. of eyes Preoperative elevated intraocular pressure Postoperative elevated intraocular pressure Hypotony Intraoperative break Schlieren Peripheral trough dissection
No Light Perception (no. of eyes)
12
26
2
2
1
1
2
7
13-18
7-12
19-24
Age (Months)
Fix and Follow (no. of eyes)
o
0-6
Fig 4. Postoperative anatomic success as a function of the child's age at time of surgery. 45 40
3
1
2
5
10
35 Vl
Q)
25
0
20
'#:
15
- Total Eyes - Visual Improvement (Fix and Follow) Visual Decrease (No Light Perception)
o -
30
>.
w
_ ~
10
plications could be determined. Pre- and postoperative factors and operative complications are examined in Table 4 for those eyes in which vision improved to fix and follow or declined to no light perception. Preoperative lOP was elevated in 2 (8%) of 12 eyes in the visual improvement group and in 2 (8%) of 26 eyes in the visual failure group. Postoperative lOP elevation requiring treatment occurred in 1 (8%) of 12 eyes which visually improved and in 3 (11 %) of 26 eyes that declined to no light perception. Hypotony was recorded in one eye with no light perception. Massive bleeding, which could not be controlled, infection, and complications of anesthesia were not encountered in either group. Intraoperative peripheral retinal breaks were reported in 1 (8%) of 12 eyes with visual improvement and in 2 (8%) of 26 eyes with no light perception. All eyes with known breaks remained detached postoperatively. Schlieren, the streaks seen when two clear fluids of different optical densities mix, were noted without an observable retinal break in two eyes (17%) in the improved group and in five eyes (20%) in the no light perception group. Dissection of the peripheral retinal trough 7 was possible in 7 (58%) of 12 eyes in the visually successful category and in 10 (39%) of 26 eyes with no light perception (P = 0.346). The child's age at the time of vitreous surgery was considered and compared with anatomic success in Figure 4. Forty-five (42%) of the 107 eyes in which the final postoperative retinal configuration could be determined had vitreous surgery by 6 months of age. In this group, anatomic success was obtained in 12 eyes (27%). Anatomic 824
5 0
0-6
7-12
13-18
19-24
Age (Months)
Fig S. Visual outcome as a function of the child's age at the time of surgery. Patients without visual acuity change are not plotted.
success in the 62 eyes of children older than 6 months was achieved in 38 eyes (61 %). Figure 5 compares the child's age at surgery to visual outcome for those 101 eyes in which preoperative and final postoperative visual acuity were accurately obtained. In children who had surgery by 6 months of age (n = 38), one eye (3%) improved to fix and follow vision. In children older than 6 months of age at the time of surgery (n = 63), vision improved in 11 eyes (17%) to the level of fix and follow. In children who underwent surgery by age 6 months or younger, vision decreased to no light perception in 13 (34%) of 38 eyes. No light perception was the final visual outcome in 13 (21 %) of 63 eyes in those children operated on at ages greater than 6 months of age (P = 0.177). The percentage of eyes with improved visual acuity (fixation and following) as a function of retinal attachment (anatomic success) was determined for the two age groups. For children 6 months of age or younger, 1 (8%) of 12 eyes with known attached retinas had improved vision, and in children over 6 months of age, 11 (29%) of 38 eyes with anatomic success also had improved visual acuity. Plus disease, defined as abnormal dilation and tor-
ZILIS et al
•
VITREOUS SURGERY FOR ADVANCED ROP
tuosity of retinal vessels,l was identified in eight eyes preoperatively. All cases occurred in children younger than 6 months of age at the time of surgery. Partial retinal attachment was possible in two eyes (25%). Improved vision did not occur postoperatively, and two eyes had no light perception. Twenty-seven eyes in the stage 5 group underwent a reoperation involving additional vitreous surgery. In 17 eyes with total RD, reoperation resulted in at least partial posterior attachment in five eyes. In ten eyes with partial attachment before reoperation, only one eye gained complete posterior attachment, although often with reoperation, further release of traction with retinal unfolding was achieved. Overall, vision improved in only one patient (4%) and decreased in four (15%).
DISCUSSION Vitreous surgery for RD in advanced ROP continues to evolve. 3,7-9 For example, we have learned that a more anterior approach, 7 entering the eye in front of the iris combined with lentectomy, results in fewer tears in the anteriorly detached retina and pars plana epithelium. Our efforts in these small eyes have been aided greatly with the modification and new design of surgical instrumentation. With the knowledge that the adequate release of traction is of paramount importance in these eyes, we have become more aggressive in our attempts to remove proliferations, particularly in the region of the peripheral trough. 7 However, this approach to membrane removal is tempered by the knowledge that retinal breaks in these eyes can be a devastating complication. In this report, we analyzed the anatomic and visual results of our surgical approach to stages 4 and 5 ROP over the past 10 years. Trese8 in 1984 reported that 18 (40%) of 40 eyes with stage 5 ROP were attached 6 months after surgery and that closed funnels had only a 26% anatomic reattachment rate. In 1986, we reported4 a 43% rate of anatomic success in 58 eyes of children with combined stages 4 and 5 ROP operated on by 1 year of age. Our current, larger series of 135 children showed an anatomic success of 40% (49 of 121 eyes) with stage 5 ROP compared with our previous 1986 report in which 33% (15 of 46 eyes) with stage 5 ROP were surgically reattached. With increasing surgical sophistication, more difficult cases have been attempted. As an example, in this series, the narrow/narrow preoperative funnel configuration6 represents 40% (36 of 92 eyes) of stage 5 eyes compared with only 16% (7 of 45 eyes) in 1986. As expected,3,8 in this current series, the wide/wide funnel configuration had the best attachment rate, 63% (19 of30 eyes), and the narrow/narrow category had the poorest, 31 % (11 of 36 eyes). Anatomic success as a function of a child's age at the time of vitreous surgery showed that only 27% (12 of 45 eyes) of infants 6 months of age or younger were successfully attached compared with 61 % (38 of 62 eyes) of those older than 6 months at the time of surgery. We can speculate that in this nonrandomized, retrospective anal-
ysis, there may be a bias in the selection process of children of different ages. Older ages may represent more favorable cases since eyes which were already blind or had glaucoma were not selected for surgery. Further, the clinical activity of the disease and the risk of reproliferation may be greater in younger children. 9 In this report, all of the eight eyes of children with plus disease were younger than 6 months at the time of surgery. Despite better anatomic results, only a small percentage of children have significant postoperative visual improvement. Unfortunately, in these infants, the accuracy of visual acuity testing is limited. Even full-term infants with presumed normal visual and neurologic development tested with Teller preferentiallooking iO seldom attain reproducible 6/60 levels of visual acuity until 4 months of age. II Therefore, it is not surprising that visual acuity testing in premature infants with variable degrees of neurologic delay and severe retinopathy will yield low and sometimes inconsistent results. U sing the broad categories of: (1) purposeful, fixation, and following vision; (2) primitive, light perception; and (3) no light perception, we found that improved postoperative vision to the level of fixation and following occurred in 35% (5 of 14 eyes) with stage 4 ROP and in only 12% (12 of 101 eyes) with stage 5 ROP compared with preoperative vision (Fig 1). Vision decreased to no light perception postoperatively in 2 (14%) of 14 eyes with stage 4 and in 26 (26%) of 101 eyes with stage 5 ROP (Fig 1). Of special interest were those six eyes in which surgery was performed when no consistent light perception could be demonstrated preoperatively. Four ofthese eyes showed improvement to light perception, and two remained with no light perception. This highlights our problems with the accurate assessment of low vision in these infants. Retinal attachment in stage 5 eyes was significantly more likely to result in improved visual acuity (P = 0.01). Conversely, continued postoperative RD was likely to result in no light perception (P = 0.03) (Table 3). Visual improvement in stage 5 eyes occurred most frequently in the wide/wide funnel configuration with 17% attaining fixation and following acuity. Factors such as lOP, hypotony, and surgical complications in the visually improved (fix and follow) category were compared with the visual failure category (Table 4). No significant differences were found, although the numbers of patients are small. In autopsy eyes of children with stage 5 ROP, severe photoreceptor inner segment loss and retroretinal membrane formation has often been observed l2 ,13 which was inapparent clinically. These chronic changes may account, in part, for the many eyes which were attached successfully without improvement in postoperative visual acuity, Therefore, earlier surgical intervention after RD should enhance visual results. Evidence in the pediatric literature ll suggests that in cases of bilateral congenital cataracts, surgical intervention before 8 weeks of life increases the chances of visual rehabilitation. Wiesel and Hubel 14 showed that irreversible amblyopia with loss of geniculocortical neurons occurs 825
OPHTHALMOLOGY
•
JUNE 1990
in kittens occluded for the first 8 and 12 weeks of life, respectively. However, the damage induced by occlusion for shorter periods of time may be reversible. Furthermore, is the potential for vision dependent on a certain period of retinal attachment before detachment occurs? Why then did children in this study show less postoperative visual acuity improvement if their surgery was performed at 6 months of age or younger (1 of 38 eyes or 3%) than if they were operated on after 6 months of age (11 of 63 eyes or 16%)? Because fewer eyes were reattached in the younger age group, those cases with visual improvement as a function of retinal reattachment for each group was determined. Only 8% of attached retinas in the younger group had improved postoperative visual acuity compared with 29% of the older group (P = 0.02). The reasons for such results remain unknown. This observation may be biased because of the relatively small numbers of patients and arbitrary selection process in this retrospective series, but we also may speculate that other factors might playa role. Is the regenerative capacity of the retina dependent on a certain level of development? Do detachments that occur before adequate macular developmene s,16 result in more profound amblyopia? Flynn 1? noted that if the conceptual age of these premature infants is calculated, these children are actually months younger than full-term infants at the time of examination. For example, a child with a gestation of only 26 weeks who undergoes surgery at 4 months of age has a conceptual age of only 42 weeks at the time of surgery. At that age, macular development may be incomplete 1S ,16 and perhaps may contribute to the poor functional results obtained. Although it was our observation that reoperation involving additional vitreous surgery usually provided additional release of traction with further unfolding of the retina, posterior reattachment occurred in only 22% (6 of 27 eyes), and vision improved in only one eye (4%). We therefore have become more reluctant to recommend reoperations. Vitreous surgery for advanced ROP, particularly stage 5, has led to increases in the number and type of anatomic successes, yet visual improvement remains extremely low, both in percentage and level of improvement for all categories of stage 5 ROP. Although our data showed that the anatomic and especially the visual outcome of surgery in children younger than 6 months of age was poorer than in older children, visual results in all ages are too low. Therefore, we have not abandoned the concept of early intervention but instead argue that fundamental changes in our approach are necessary if the prognosis is to improve. Thanks largely to the Cryo-ROP trial,l enhanced surveillance of high-risk infants with appropriate intervention at the threshold level should decrease the numbers of chil- .
826
•
VOLUME 97
•
NUMBER 6
dren who advance to RD. In those children who do develop partial RD despite cryotherapy, scleral buckling may be beneficial, and a clinical trial is being considered. In addition, cryotherapy appears to lessen the vascular activity (plus) of the disease. Therefore, early vitreous surgery in infants who have been previously treated with cryotherapy before their RD may lead to greater successes in the future.
REFERENCES 1. Cryotherapy for Retinopathy of Prematurity Cooperative Group. MUlticenter trial of cryotherapy for retinopathy of prematurity: preliminary results. Arch Ophthalmol1988; 106:471-9. 2. Tasman W. Multicenter trial for cryotherapy for retinopathy of prematurity [Editorial]. Arch Ophthalmol1988; 106:463-4. 3. Machemer R. Closed vitrectomy for severe retrolental fibroplasia in an infant. Ophthalmology 1983; 90:436-41. 4. Chong LP, Machemer R, deJuan E. Vitrectomy for advanced stages of retinopathy of prematurity. Am J Ophthalmol1986; 102:710-6. 5. Friberg TR, Tano Y, Machemer R. Streaks (Schlieren) as a sign of rhegmatogenous detachment in vitreous surgery. Am J Ophthalmol 1979; 88:943-4. 6. The International Committee for the Classification of the Late Stages of Retinopathy of Prematurity. An international classification of retinopathy of prematurity: II. The classification of retinal detachment. Arch Ophthalmol1987; 105:906-12. 7. deJuan E Jr, Machemer R. Retinopathy of prematurity: surgical technique. Retina 1987; 7:63-9. 8. Trese MT. Surgical results of stage V retrolental fibroplasia and timing of surgical repair. Ophthalmology 1984; 91 :461-6. 9. Charles S. Vitreoretinal surgery for retinopathy of prematurity. In: Flynn JT, Phelps DL, eds. Retinopathy of Prematurity: Problem and Challenge. New York: Alan R. Liss, 1988; 287-93. (Birth defects original article series; v. 24, no. 1) 10. Teller DY, Morse R, Borton R, Regal D. Visual acuity for vertical and diagonal gratings in human infants. Vision Res 1974; 14:1433-9. 11. Rogers GL, Tishler CL, Tsou BH, et al. Visual acuities in infants with congenital cataracts operated on prior to 6 months of age. Arch Ophthalmol 1981; 99:999-1003. 12. Foos RY. Retinopathy of prematurity: pathologiC correlation of clinical stages. Retina 1987; 7:260-76. 13. deJuan E Jr, Machemer R, Flynn JT, Green WR. Surgical pathoanatomy in stage 5 retinopathy of prematurity. In: Flynn JT, Phelps DL, eds. Retinopathy of Prematurity: Problem and Challenge. New York: Alan R. Liss, 1988; 281-6. (Birth defects original article series; v. 24, no. 1) 14. Wiesel TN, Hubel DH. Comparison of the effects of unilateral and bilateral eye closure on cortical unit responses in kittens. J Neurophysiol 1965; 28:1029-40. 15. Isenberg SJ. Macular development in the premature infant. Am J Ophthalmol1986; 101 :74-80. 16. Hendrickson AE, Yuodelis C. The morphological development of the human fovea. Ophthalmology 1984; 91 :603-12. 17. Flynn JT. Acute proliferative retrolental fibroplasia: multivariate risk analysis. Trans Am Ophthalmol Soc 1983; 81 :549-91.