Clinico-Demographic Profile and Outcomes of 25-Gauge Vitrectomy in Advanced Stage 5 Retinopathy of Prematurity

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Graefe's Archive for Clinical and Experimental Ophthalmology (2021) 259:1695–1701

https://doi.org/10.1007/s00417-020-05063-2

RETINAL DISORDERS

Clinico-demographic profile and outcomes of 25-gauge vitrectomy


in advanced stage 5 retinopathy of prematurity
Renu P. Rajan 1 & Naresh Babu Kannan 1 & Sagnik Sen 1 & Lavanya C 1 & Soumya Jena 1 & Karthik Kumar 1 &
P. Vijayalakshmi 2 & Kim Ramasamy 1

Received: 12 May 2020 / Revised: 6 October 2020 / Accepted: 21 December 2020 / Published online: 6 January 2021
# The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature 2021

Abstract
Background Stage 5 retinopathy of prematurity is a difficult condition to treat despite technological advances in vitreous surgery.
Methods A retrospective chart review of all consecutive cases of stage 5 ROP was performed between December 2016 and
December 2018, and 21 babies were included for assessment of surgical outcomes using a modified vitrectomy technique. Data
extracted from documents included demography, ROP screening status, preoperative prophylactic therapy, clinical presentation,
surgery performed, and postsurgical outcomes.
Results Out of the 21 babies, ophthalmologist screening was done in 42.9%. Mean birth weight was 1185 ± 222.4 g with a
mean gestational age of 29.86 ± 2.0 weeks and mean post-menstrual age of 44.55 ± 9.82 weeks. Lesser than stage 5 disease
was seen in 16.7% of eyes and they were managed accordingly. Seventy percent of babies had bilateral disease. 21 eyes
underwent 25-gauge pars plicata vitrectomy using a modified technique. After an average follow-up duration of 6.33 ± 2.18
months, the final macular attachment rate was 19%. Anteriorly closed-posteriorly closed type configuration of retinal
detachments had a poorer outcome. Fix and follow visual acuity was achieved in 23.8% of eyes, while 57.1% of eyes
had a perception of light.
Conclusions Management of stage 5 ROP is mostly surgical; however, the risk of ending up with a poor vision or vision loss is
high, irrespective of whether surgery is performed. The modified surgical technique with a spacer described in this study may
help in better manipulation of instruments inside the vitreous cavity.

Keywords ROP . Stage 5 ROP . Pars plana vitrectomy

Key messages:

A lot of stage 5 ROP babies in developing countries might not have undergone ROP screening, due to lack of
accessibility to healthcare and the outcomes of stage 5 ROP have been recorded to be poor.

The pattern of ROP in developing countries like India is different from the west, with older and heavier babies
presenting with more severe and advanced disease.

This paper describes a novel method of vitreoretinal surgery in Stage 5 ROP eyes, however the final anatomical
success after surgery is comparable to what has been described from the west.

* Sagnik Sen Introduction


riksag@gmail.com
Retinopathy of prematurity (ROP) has gained the status of an
Extended author information available on the last page of the article epidemic in developing nations. Survival of preterm infants
1696 Graefes Arch Clin Exp Ophthalmol (2021) 259:1695–1701

has increased because of improvement in neonatal care. patterns of disease and association with aggressive posterior
However, proper protocol-based screening of ROP still does ROP (APROP). With advances in surgical technology and
not reach all neonates in need. This can be attributed to various techniques, outcomes of surgery may also differ or improve,
factors like lack of awareness regarding disease, lack of acces- and in this respect, our study may be considered crucial.
sibility to the nearest ophthalmic care center, and failure of
screening chain and follow-up. In Asian countries, ROP might
begin at higher gestational age (GA) than in the West [1]. India
also faces a challenge of heavier babies developing progressive Methods
ROP, with threshold ROP occurring in babies with birth weight
(BW) > 2000 g, while US studies report minimal treatable ROP Retrospectively, the medical records of all consecutive cases
in babies with BW > 1500 g at birth [1–3]. Authors have ob- of stage 5 ROP presenting to our tertiary care ophthalmic
served that in India, aggressive posterior ROP may also be center from December 2016 to December 2018 were
common in heavier BW babies with almost 16% of babies reviewed. The study strictly followed the principles of the
developing APROP having BW > 1500 g. (Shah et al.: mean Declaration of Helsinki and was cleared by the Institutional
BW—1554 g, mean GA—31.75 weeks; Sanghi et al.: mean Ethics Committee. The data collected included details on GA,
BW—1260 g, mean GA—29.75 weeks) [4, 5]. Some studies gender, BW, age and weight at presentation, referral/screening
have found that APROP may occur even in larger preterm details, history of neonatal intensive care unit (NICU) stay,
babies with mean BW of 1500–2000 g, mostly because of oxygen therapy, mechanical ventilation, and treatment sought
unblended oxygen therapy [4]. Recently, Dwivedi et al. have until presentation. The data entered included the details re-
observed that 16.6% of babies screened had advanced ROP corded in the neonatal and/or ophthalmic screening records
(stages 4 and 5), with mean GA of 31 weeks and BW 1340 g, and parental recall. Also, the data related to the surgical man-
and almost 10% of severe ROP babies had GA > 34 weeks [6]. agement of these eyes, intraoperative and postoperative
Most developing countries do not have a well-established follow-up details were recorded.
national program targeting ROP. Hence, a large proportion of
babies at risk never get screened for ROP, and many eyes with
preventable disease may progress to advanced stages. Proper Ophthalmic examination
neonatal care and protocol-based screening can help reduce
the incidence of any stage of ROP, treatable disease, and ag- All infants underwent anterior and posterior segment exami-
gressive posterior ROP [7]. Although most cases ideally nation. Anterior segment examination involved careful
should resolve with observation or laser photocoagulation checking for the corneal clarity, anterior chamber depth, pu-
therapy, it is not uncommon to find infants presenting with pillary and iris status, and clarity of the crystalline lens.
advanced and complicated stages of ROP (namely stages 4 Posterior segment examination was performed using both in-
and 5) in developing nations. At these stages, laser therapy direct ophthalmoscopy with a + 28-D/+ 20-D lens and Retcam
does not hold much importance and surgical modalities need III (Clarity Medical Systems Inc., Pleasanton, CA, USA)
to be considered. when possible. Dilatation was achieved using phenylephrine
Surgery for ROP has evolved over the years, with scleral 2.5% and tropicamide 0.4% eye drops, put twice 15 min apart.
buckling being an important surgical modality initially. Eyelid skin of all babies was carefully cleaned after drop in-
However, buckling was seen to be associated with secondary stillation, to reduce systemic absorption. All infants were ex-
effects like axial length elongation, along with chances of amined by a retina specialist well-experienced in ROP screen-
amblyopia later, and hence slowly decreased in popularity. ing, who documented zone, stage, and extent of ROP in terms
For the past decade, microincision vitrectomy surgery of clock hours and the presence of pre-plus or plus disease,
(MIVS) has revolutionized the outcomes, more so for stage according to the international classification of ROP [10].
4 ROP. Stage 5 ROP eyes do not seem to perform well with
surgical management, with or without the removal of the lens
[8, 9]. Hence, management of these eyes is a major challenge Ultrasonography
for developing nations today.
This study was designed to evaluate the risk factors, out- Ultrasonography (A and B scans) was performed in all stage 5
comes, and factors predictive of surgical outcome of stage 5 ROP eyes by a trained professional and confirmed by a trained
ROP eyes. With stage 5 ROP being a rare disease, not many ophthalmologist and the three best images taken were record-
surgical series are available from this subcontinent. Moreover, ed. The following types of retinal detachment (RD) were de-
the stage 5 ROP eyes seen in the developing nations may fined: anteriorly open-posteriorly closed, anteriorly open-
behave differently than those described in the west, due to posteriorly open, anteriorly closed-posteriorly open, and ante-
development in older and heavier babies or more aggressive riorly closed-posteriorly closed.
Graefes Arch Clin Exp Ophthalmol (2021) 259:1695–1701 1697

Protocol for pars plana vitrectomy Results

All eyes deemed fit for surgery underwent standard three-port Demography
25-gauge vitrectomy by any one of two experienced surgeons
(N.B.K. and R.P.R.). Sclerotomies were made 0.5 to 1.0 mm Twenty-one babies presented to our clinic with advanced
posterior to the limbus through pars plicata. In all surgeries, a stage 5 ROP in at least one eye from December 2016 to
spacer (2-mm × 2-mm piece of #42 silicone encircling band, December 2018. Sixteen babies (76.2%) were born in the state
1.25-mm thickness) was used between the sclera and the base of Tamil Nadu, 1 (4.8%) in Andhra Pradesh, 2 (9.5%) in
of the 25-gauge surgical cannulas. This was done to maximize Pondicherry, and 2 (9.5%) in Kerala.
the space for surgical manipulation inside small infant eyes Of the 21 ROP babies, 7 (35%) were male and 14 (65%)
[11]. Surgeries were performed under a binocular indirect were female. Mean GA overall was 29.86 ± 2.0 weeks (range,
ophthalmic microscope (BIOM) with a Constellation 25- 26–33 weeks; median = 29 weeks) and BW was 1185 ±
gauge vitrectomy instrument (Alcon, TX, USA), at intraocular 222.4 g (range, 990–1700 g). Overall, 2 infants (9.5%) had
pressure of 15 mm Hg and cutting speed of 5000 per minute. > 1500 g BW, 2 infants (9.5%) had > = 32-week GA, and 2
The goal of the surgery was to relieve the traction between the infants (9.5%) were just completing 32 weeks of gestation.
ridge and ciliary body, lens, and optic disk. Only 1 infant had both > 1500 g BW and > 32-week GA.
Lensectomy was performed for cases in which the retina None of our cases had a BW of > 1750 g or GA of > 34 weeks.
with attached membranes was very close to the posterior sur- Mean post-menstrual age (PMA) was 44.55 ± 9.82 weeks
face of the lens where manipulation was difficult. Anterior (range, 34–71 week; median = 42 weeks) and the babies were
membrane dissection was initiated with microvitreoretinal brought to our center after a mean duration of 15.05 ± 11.49
blade and segmentation attempted using MIVS scissors, for- weeks (range, 4–43 weeks; median = 12 weeks) after birth.
ceps, and cutter after identifying a dissection plane. Limited
vitrectomy was performed to release tractional elements. NICU care
Viscocohesive agent was injected at the end of the surgery
to aid in the further opening of the funnel. Complete reattach- Seventeen babies out of a total of 21 had received NICU care
ment at the end of surgery was not attempted and and out of these, 12 babies were referred for ROP screening.
endotamponade with silicone oil or endolaser was not per- The rest 4 babies did not receive NICU care or ophthalmolo-
formed in any of the cases. During the postoperative period, gist referral and presented to us directly with stage 5 ROP. Out
a topical antibiotic and steroid combination drop was used of 17 babies who received NICU care, 9 (52.9%) babies were
four times a day, tapered over 1 month. screened by an ophthalmologist outside. The rest 8 (47.1%)
babies were directly referred to us from the NICUs. The aver-
age number of days in NICU was 35.3 ± 19.4 days (range, 7–
Follow-up
90 days). Moreover, they were given oxygen supplementation
for a mean duration of 22.9 ± 14.5 days (range, 3–45 days).
All operated infants were followed up routinely on day 1 after
Only 1 child had received laser treatment outside, while 1
surgery, at 1 week, 1 month, and as needed thereafter. All
child was lost to follow-up after screening. The commonest
babies, including non-operated cases were referred to the pe-
complaints by the parents of 12 babies who directly came to
diatric ophthalmology department for low vision rehabilita-
our center without prior screening (8 who received NICU care
tion. Anatomical success was measured as the percentage of
and 4 who did not) were inability to fix at the mother’s face
eyes that attained posterior pole attachment on ultrasound at
(10/12), whitish reflex (6/12), and abnormal eye movements
the final follow-up. Functional outcomes were measured as
(5/12).
the presence of perception of light, “fixes and follows” visual
acuity, or “central-steady-maintained” fixation, etc.
Clinical presentation

Data analysis A total of 35 eyes had stage 5 ROP. Fourteen babies (67%)
had bilateral stage 5 ROP (28 eyes). In the 7 babies having
Data were entered into Microsoft Office Excel 2013 unilateral stage 5 disease, three fellow eyes had stage 3 ROP
(Microsoft, Redmond, WA) and analyzed using Stata (Stata and four fellow eyes had stage 4A ROP. Of the 35 eyes with
Statistical Software: College Station, TX, Stata Corp LP). stage 5 ROP, 17 eyes (48.5%) presented with leukocoria, 3
Variables were compared using chi-square or Fisher exact test, eyes (8.6%) had a corneal opacity, 20 eyes (57.1%) had a
Student t test, or Mann Whitney test wherever applicable. A shallow anterior chamber, 6 eyes (17.1%) had posterior
two-tailed p value of < 0.05 was considered statistically synechiae to the lens, and 4 eyes (11.4%) had
significant. microphthalmos. Sixteen eyes (45.7%) presented with
1698 Graefes Arch Clin Exp Ophthalmol (2021) 259:1695–1701

nystagmus. The fundus could not be assessed clinically in dissection, which was controlled by temporarily increasing
sixteen eyes because of poorly dilating pupils and/or posterior the intraocular pressure and aspiration of the blood.
synechiae in 10 eyes (28.6%) and corneal opacity in 6 (17.1%)
eyes. The types of retinal detachment detected were anteriorly Postoperative outcomes
closed-posteriorly open (8.6%), anteriorly open-posteriorly
closed (31.4%), and anteriorly closed-posteriorly closed The average duration of postoperative follow-up was 6.33 ± 2.18
(57.1%). months (range, 3–12 months; median = 6 months). None of the
Fourteen eyes (40%) were judged unfit for surgical interven- eyes developed postoperative bleeding. Table 2 summarizes the
tion. Among them, 50% of eyes had anteriorly closed-posteriorly retinal reattachment status after surgery at the immediate and
closed configuration of the retinal detachment and 35.7% had final follow-ups. Although 50% of eyes with anteriorly closed-
anteriorly open-posteriorly closed configuration. Three of these posteriorly open configuration showed anteriorly open-
eyes (20%) had corneal opacities, 9 (60%) had shallow anterior posteriorly closed configuration at immediate postoperative fol-
chambers, 5 (33.3%) eyes had posterior synechiae to the lens, low-up, both these eyes had anteriorly closed-posteriorly closed
and 3 (20%) eyes had microphthalmos. One eye had an associ- configuration at final follow-up. Eyes having anteriorly open-
ated organized vitreous hemorrhage along with anteriorly closed- posteriorly closed RD preoperatively ended up with 50% having
posteriorly closed configuration of RD. anteriorly open-posteriorly closed configuration and 50% having
attached macula (on ultrasound) at final follow-up. Eleven eyes
having anteriorly closed-posteriorly closed configuration ended
Surgical details up in 54.5% having anteriorly open-posteriorly closed configu-
ration. The final macular attachment rate was 19%. On functional
Of the 35 eyes, 21 eyes (60%) underwent surgery (Table 1). evaluation at final follow-up, 12/21 (57.1%) eyes achieved a
Five babies (23.8%) underwent bilateral surgeries. In 4 babies vision of perception of light, 5/21 (23.8%) eyes achieved good
with bilateral stage 5 ROP, only one eye was considered for fixation and following movements, and 4/21 (19%) ended in no
surgical management, since the fellow eyes were found to perception of light. Three eyes (60%) that achieved good fixation
have advanced and untreatable disease. The average age at and following movements had attached macula at final follow-
presentation for the 21 operated eyes was 40.0 ± 5.3 weeks up. All 4 eyes which had no perception of light had closed-closed
PMA against an average of 46.8 ± 8.06 weeks PMA in the configuration (Table 2).
unoperated eyes. Fourteen eyes underwent lensectomy simul-
taneously during vitrectomy. Three babies had a non-
advanced ROP stage (stage 3 and below) in the fellow eye, Discussion
for which photocoagulation was done with close observation.
In 4 others, the fellow eyes had stage 4A ROP, for which Retinopathy of prematurity is a challenging disease for oph-
necessary surgical management was performed. None of the thalmic practitioners worldwide, not only because of its com-
eyes developed any iatrogenic hole during surgery. Two eyes plexity in pathogenesis but also because of associated medical
developed intraoperative bleeding during membrane issues, including prematurity and low birth weight. Although
the majority of ROP regresses spontaneously, advanced stages
(4 and 5) seem to be much more prevalent in the developing
Table 1 Surgical management of the ROP study population countries, reported as the third epidemic of ROP [12, 13].
Although the incidence of ROP is rising worldwide due to
Number Percentage improved perinatal care, safe and effective laser treatment of
non-advanced ROP has reduced end-stage ROP incidence in
Total number of eyes with ROP 42
developed countries like the USA [14–16]. Providing metic-
Total number of eyes with stage 5 ROP 35/42 83.3
ulous medical management in NICUs, with timely screening
No intervention 14/35 40
as per protocol, can reduce the occurrence of ROP.
Intervention
Lack of knowledge and awareness regarding the prevention
Pars plana vitrectomy 21/35 60
and treatment of ROP among parents plays a major role in
Pars plana vitrectomy with lensectomy 14/21 66.7
health-seeking behavior and compliance. In our series, the chil-
Surgery along with bevacizumab injection 5/21 23.8
dren were brought after a mean period of almost 2 months after
Fellow eyes—other than stage 5 ROP 7/42 16.7
birth and the longest period was 10 months. The number of girl
Zone 3 disease less than/equal to stage 3/7 42.8
children suffering from stage 5 ROP in our series was more than
3 without plus
Stage 4a disease 4/7 57.1 males and this may reflect an underlying social trend of preferred
Eyes with stage 5 ROP and plus disease 5/35 14.3 attention to the male child, which is common in rural parts of the
country. Outcomes of ROP depend on early detection and
Graefes Arch Clin Exp Ophthalmol (2021) 259:1695–1701 1699

Table 2 Anatomical outcomes of retinal detachment surgery of stage 5 ROP eyes

Preoperative Total Operated Unoperated Postoperative retinal status Postoperative functional-status


retinal detachment at final follow-up
configuration Immediate Final follow-up
postoperatively

Anteriorly Anteriorly Anteriorly Anteriorly Attached


open- closed- open- closed- posterior
posteriorly posteriorly posteriorly posteriorly pole
closed closed closed closed

Anteriorly 2 2 0 1 1 0 2 0 No PL = 1 with close-close


closed-- configuration
posteriorly PL+ = 1 with close-close
open configuration
Anteriorly 12 8 4 6 2 4 0 4 Fixation and following
open-- movements = 3 with attached
posteriorly macula, 2 with open-close
closed configuration
PL+ = 1 with attached macula, 2
with open-close
configuration
Anteriorly 21 11 10 7 4 6 5 0 PL+ = 6 with open-close
closed-- configuration, 2 with
posteriorly close-close configuration
closed No PL = 3 with close-close
configuration –
Total 35 21 14 14 7 10 7 4 No PL = 4
PL+ = 12
Fixing and following
movements = 5

PL, perception of light

effective management and follow-up of babies, which is highly likelihood of reattachment, making the overall long-term suc-
reliant on a strong collaboration between pediatricians, ophthal- cess rate of surgery poor [8, 9, 18]. Preoperative configuration
mologists, and paramedical personnel. Prior laser photocoagula- of RD may be a prognostic factor for final attachment [19]. In
tion seems very important for earlier stages of surgical ROP our series, we found that the outcomes of anteriorly closed-
cases, e.g., stage 4 ROP, by helping in the stabilization of periph- posteriorly closed RD were poorer than for the other configu-
eral retina and halting/regressing RD. Among our babies, only 1 rations, similar to observations by Cusick et al. (Table 2) [9].
(5.2%) had received laser photocoagulation. Prior treatment was The number of eyes in the current series is not high enough to
given in 10.4% in the series described by Gopal et al. and 22% in strongly suggest this association, and the same may be evalu-
the Cusick et al. study [9, 17]. ated more effectively in larger longitudinal studies. In contrast
Management of stage 5 ROP is mostly surgical; howev- to Cusick et al.’s retrospective analysis of surgical outcomes
er, such babies are at a high risk of losing vision, irrespec- over 25 years of evolving vitrectomy techniques, our study
tive of surgery. Determining the appropriate time for sur- evaluated a single advanced technique of microincision vit-
gery in stage 5 ROP eyes is debatable. In our series, sur- rectomy done over 2 years. Outcomes of 20-G rigid instru-
geries were performed at a median duration of 42 weeks, ment surgeries and 23–25-G MIVS are expected to be differ-
which is comparable to the international data [9]. Surgery ent, with the latest generation instruments being more efficient
is generally restricted to limited dissection of membranes [16]. In this series, we avoided creating iatrogenic breaks due
and vitreous. In this regard, 25-gauge instruments offer a to limited length and movement of instruments inside the eye
wide range of flexibility and easy manipulation in small and achieved adequate membrane dissection; however, the
pediatric eyes. The technique of using a piece of #42 band final anatomical success rate was 19%. The success rate of
as a spacer helped increase the field of movement inside surgery in stage 5 eyes ranges from 13% as reported by
small eyes by reducing the shaft of the 25G cutter and Choi et al. to 28% reported by Cusick et al. [20]. Kondo
increased the rigidity of the instrument [11]. et al. observed that even after successful reattachment of the
It is apparent from the results of our series and also from retina, a repeat detachment would occur in 22% of stage 5
previous literature that ROP stage 5 eyes may show very poor eyes [18].
1700 Graefes Arch Clin Exp Ophthalmol (2021) 259:1695–1701

In our series, 23.8% of eyes achieved higher than percep- Institutional review board statement This study was reviewed and ap-
proved by the ethics committee of the Aravind Eye Hospital.
tion of light visual acuity. Cusick et al. noted that 85% of stage
5 ROP eyes ended up with no perception of light, 14% of eyes
Informed consent statement Patients were not required to give in-
could achieve form visual perception, while only 4% of eyes formed consent to the study because the analysis used anonymous clinical
achieved visual acuity better than 5/200 [9]. Among the eyes data that were obtained after each patient agreed to treatment by written
which had attached macula, only 16% had visual acuity better consent.
than 5/200 and 11% could not perceive light. Choi et al. found
Consent for publication All authors have given their consent for publi-
perception of light present in 48% of stage 5 ROP eyes after
cation and authorship.
vitrectomy [20]. In the series by Karacorlu et al., 65% of eyes
achieved visual acuity only in the range of perception of light,
no perception or fixing and following vision [21]. This overall
poor functional improvement reflects the poor prognosis of
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Late recurrence of retinal detachment following successful vitreous

Affiliations

Renu P. Rajan 1 & Naresh Babu Kannan 1 & Sagnik Sen 1 & Lavanya C 1 & Soumya Jena 1 & Karthik Kumar 1 &
P. Vijayalakshmi 2 & Kim Ramasamy 1

1 2
Department of Vitreo-Retina, Aravind Eye Hospital, Madurai, India Department of Pediatric Ophthalmology, Aravind Eye Hospital,
Madurai, India

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