Stickler Syndrome (SS): Laser Prophylaxis for Retinal Detachment (Modified Ora Secunda Cerclage, OSC/SS)

Abstract

Purpose
To introduce a novel technique of encircling laser prophylaxis (ora secunda cerclage Stickler syndrome, OSC/SS) to prevent rhegmatogenous retinal detachment (RRD) in Stickler syndrome eyes.

Patients and Methods
After first eye RRD at age 50 and at age 18, respectively, a 53-year-old father and his 22-year-old son with type 2 SS (STL2) gave informed consent and underwent OSC/SS prophylaxis, performed in each fellow eye. A 26-year-old STL2 daughter then suffered first eye retinal detachment and similarly chose fellow eye OSC/SS prophylaxis. A second son, 28 years of age with STL2, chose OSC/SS prophylaxis in both eyes.

Results
The three OSC/SS treated fellow eyes have gone 12 years, 11 years, and 8 years without RRD. STL1 and less common STL2 eyes are known to have a similar rate of RRD, and 80% of STL1 fellow eyes develop RRD at a median of 4 years in the absence of prophylaxis. Moreover, five of six (83%) known STL2 family members suffered RRD, only the STL2 son with bilateral OSC/SS remaining bilaterally attached. All five OSC/SS treated eyes (average 8.7 years post-prophylaxis) retained preoperative visual acuity of 20/20 to 20/30, with an average, asymptomatic reduction of meridional field in each eye to 50 degrees. In contrast, in the three eyes having suffered RRD prior to presentation, visual acuity ranged from 20/125 to 8/200 and average meridional field was 29 degrees.

Conclusion
Encircling grid laser (OSC) modified in Stickler eyes to encompass the ora serrata and extend posteriorly to and between the vortex vein ampullae (OSC/SS) is a reasonable RRD prophylaxis option to offer STL1 and STL2 patients as an alternative to no treatment or less effective prophylaxis. Because of rarity and severity, the ultimate proof of safety and efficacy will likely come not from randomized trials, but from a non-randomized, prospective, cohort comparison study of such individual efforts.

Full text

CASE SERIES
Stickler Syndrome (SS): Laser Prophylaxis for
Retinal Detachment (Modied Ora Secunda
Cerclage, OSC/SS)
This article was published in the following Dove Press journal:
Clinical Ophthalmology
Robert E Morris,
1–4
Edward Scott Parma,
5
Nathaniel H Robin,
6
Mathew R Sapp,
1–4
Matthew H Oltmanns,
1–4
Matthew R West,
1–4
Donald C Fletcher,
7,8
Ronald A Schuchard,
9
Ferenc Kuhn
2,10,11
1
Retina Specialists of Alabama, Birmingham, AL,
USA;
2
Helen Keller Foundation for Research
and Education, Birmingham, AL, USA;
3
University of Alabama at Birmingham (UAB),
Department of Ophthalmology, Birmingham,
AL, USA;
4
UAB Callahan Eye Hospital,
Birmingham, AL, USA;
5
Retina Specialists of
Alabama Montgomery, Montgomery, AL, USA;
6
UAB Department of Genetics, Birmingham,
AL, USA;
7
University of Kansas Medical Center,
Department of Ophthalmology and KU Eye
Center, Kansas City, KS, USA;
8
Retina
Consultants of Southwest Florida, Ft. Myers,
FL, USA;
9
Envision Research Institute, Wichita,
KS, USA;
10
Milos Eye Hospital, Belgrade, Serbia;
11
University of Pécs, Department of
Ophthalmology, Pécs, Hungary
Video abstract
Point your SmartPhone at the code above. If you have a QR
code reader the video abstract will appear. Or use:
https://youtu.be/AzHz4xYUV_w
Purpose: To introduce a novel technique of encircling laser prophylaxis (ora secunda cerclage
Stickler syndrome, OSC/SS) to prevent rhegmatogenous retinal detachment (RRD) in Stickler
syndrome eyes.
Patients and Methods: After rst eye RRD at age 50 and at age 18, respectively, a 53-year-
old father and his 22-year-old son with type 2 SS (STL2) gave informed consent and underwent
OSC/SS prophylaxis, performed in each fellow eye. A 26-year-old STL2 daughter then suffered
rst eye retinal detachment and similarly chose fellow eye OSC/SS prophylaxis. A second son,
28 years of age with STL2, chose OSC/SS prophylaxis in both eyes.
Results: The three OSC/SS treated fellow eyes have gone 12 years, 11 years, and 8 years
without RRD. STL1 and less common STL2 eyes are known to have a similar rate of RRD,
and 80% of STL1 fellow eyes develop RRD at a median of 4 years in the absence of
prophylaxis. Moreover, ve of six (83%) known STL2 family members suffered RRD, only
the STL2 son with bilateral OSC/SS remaining bilaterally attached. All ve OSC/SS treated
eyes (average 8.7 years post-prophylaxis) retained preoperative visual acuity of 20/20 to 20/
30, with an average, asymptomatic reduction of meridional eld in each eye to 50 degrees. In
contrast, in the three eyes having suffered RRD prior to presentation, visual acuity ranged
from 20/125 to 8/200 and average meridional eld was 29 degrees.
Conclusion: Encircling grid laser (OSC) modied in Stickler eyes to encompass the ora
serrata and extend posteriorly to and between the vortex vein ampullae (OSC/SS) is
a reasonable RRD prophylaxis option to offer STL1 and STL2 patients as an alternative to
no treatment or less effective prophylaxis. Because of rarity and severity, the ultimate proof
of safety and efcacy will likely come not from randomized trials, but from a non-
randomized, prospective, cohort comparison study of such individual efforts.
Keywords: Stickler syndrome, SS, STL1, STL2, retinal detachment prevention, giant retinal
tear, encircling laser prophylaxis, Ora Secunda Cerclage, OSC, OSC/SS
Introduction
Stickler syndrome (SS) is a heterogeneous inherited disorder of collagen formation with
mutations primarily in the genes coding for type II collagen (type 1 SS, STL1, 80% of
cases) and type XI collagen (type 2 SS, STL2, <20% of cases).
1,2
It is usually inherited in
an autosomal dominant fashion and affects the eye, ear, and skeleton. A description of the
important genetic aspects of Stickler syndrome was recently provided by Robin et al.
1
Ocular-only or predominately ocular versions of SS have been increasingly
recognized, emphasizing the importance of discovery by an ophthalmologist.
3,4
Correspondence: Robert E Morris
Retina Specialists of Alabama, 2208
University Blvd, Birmingham, AL 35233,
USA
Tel +1 (205) 558-2598
Fax +1 (205) 558-2596
Email rmorris@retinanetwork.com
submit your manuscript | www.dovepress.com Clinical Ophthalmology 2021:15 19–29 19
http://doi.org/10.2147/OPTH.S284441
DovePress © 2021 Morris et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.
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work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For
permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
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Open Access Full Text Article

Ocular ndings in the STL1 and STL2 phenotype include
early-onset myopia, a mostly liquid vitreous cavity from
birth,
5
membranous (STL1) or beading (STL2) vitreous
opacities,
3
radial perivascular retinal degeneration,
4
foveal
hypoplasia,
6
early-onset cortical cataracts,
7,8
and most
importantly, retinal detachment that commonly occurs in
the rst three decades of life, even in infancy.
9
Stickler syndrome is the leading cause of inherited rheg-
matogenous retinal detachment (RRD). In Stickler patients,
RRD is usually bilateral and is often caused by a giant retinal
tear (GRT) at the ora serrata.
9
Most Stickler detachments
require multiple operations to repair, often with legally
blind visual results despite nal reattachment.
10
It is thus an
especially devastating disease for those affected.
In a series of 194 untreated STL1 patients with a mean
age of 31.3 years retrospectively reported in 2014, the
Cambridge (England) group observed an RRD prevalence
rate of 53.6% (10.3% unilateral and 43.3% bilateral), with
a median time to rst eye detachment of 18 years. In
patients who had already suffered RRD in one eye before
presenting, there was an 80% chance of a second eye
detachment, at a median of 4 years after the rst eye
detachment.
9
Against this natural course, Cambridge employed
a single row of encircling cryopexy crossing the ora serrata
for prophylaxis of GRT. Bilateral controls (no RRD) had
a 5.0-fold increased risk of an RRD (p<0.001) relative to
bilateral-treated eyes matched for age and follow-up (mean
5.9 years).
9
Prophylaxis failures (9%) occurred at an aver-
age of 5.6 years after treatment, and the mean age at treat-
ment was 21.5 years in failed cases. No long-term
complications of encircling cryopexy were observed.
The (continuing) Cambridge prophylaxis experience of
over four decades exceeds that of all other literature
reports combined. As the only entity designated as
a national center (United Kingdom) for this rare disease,
its Stickler population is diverse and its prevalence gures
are likely higher quality data than cross-study reviews of
much smaller reports having inconsistent diagnostic and
inclusion criteria.
11
For example, 87.5% of clinically diag-
nosed Cambridge STL1 patients were subsequently proven
as STL1 by genetic testing.
In apparent recognition of the potential risks of more
extensive cryopexy, Cambridge did not extend prophylaxis
posteriorly and specically stated that their treatment was
not expected to prevent tears posterior to the ora serrata. In
contrast, specically to prevent tears posterior to the ora,
we have long practiced a (standard) form of prophylactic
encircling laser retinopexy that has reliably prevented
RRD in high-risk, non-syndromic eyes. It emphasizes
grid treatment of the at-risk peripheral retina extending
from the ora serrata halfway to the vortex vein ampullae.
In effect, this creates a “second ora” behind the posterior
vitreous base which ends 3 mm posterior to the ora (Ora
Secunda Cerclage, OSC, Figure 1).
12,13
In our experience, however, the standard OSC prophy-
laxis of Figure 1 has failed to reliably prevent RRD in
Stickler syndrome. Similarly, Alsharani et al recently found
no evidence of efcacy in standard (anterior) encircling laser
prophylaxis, as 36% of 70 Stickler eyes presenting with RRD
had detached despite such prophylaxis.
14
However, OSC modied for SS (OSC/SS), to encom-
pass the ora serrata and anterior vitreous base (as per
Cambridge) and to extend more posteriorly, has been
a successful SS prophylaxis in our experience of the last
8 years. We here describe the OSC/SS technique, illu-
strated by a single-family series, that may have the poten-
tial to become more widely adopted than the Cambridge
cryopexy encirclement, based on increased provider famil-
iarity with laser retinopexy.
Patients and Methods
This retrospective case series study was determined to be
exempt from IRB approval by the Western Institutional
Figure 1 Illustration of OSC. Laser burns of moderate intensity are placed in a grid
pattern (one to two spot widths separation) extending from the ora serrata
approximately 4 mm posteriorly, in effect producing a “second ora” posterior to
the vitreous base. Used with permission of artist Stephen Gordon, copyright 2020.
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Review Board and was conducted in accordance with the
tenets of the Declaration of Helsinki for research involving
human subjects. Patients provided written informed con-
sent for their case details to be published.
A 53-year-old man and his 22-year-old son presented
with an extensive family history of RRD occurring at an
early age. Both the father and son had themselves already
suffered RRD (and redetachment) in one eye at age 50 and
18, respectively, that had been stably reattached after mul-
tiple procedures, albeit with severe vision loss. They were
in search of therapy to prevent RRD in their fellow eyes.
The man and his son stated that three local retinal
specialists had recommended no preventive treatment for
their fellow eyes. A 26-year-old daughter and a 28-year-
old son were said to be nearsighted, and both had been
treated with “spot laser” in each eye for retinal thinning.
Another, youngest son was said to have normal eyes with-
out myopia. The father had four siblings, two of whom had
suffered retinal detachment at age 17 and at age 31, while
two other siblings did not have the Stickler phenotype. His
mother had lattice degeneration, early cataract, and glau-
coma. His maternal grandfather suffered bilateral retinal
detachment by age 47 and was legally blind. The father
himself had cataract extraction at age 40, before suffering
retinal detachment in one eye at age 50.
After each losing substantial vision in one eye to RRD,
the father and son had traveled together to an eye institute
renowned for its expertise in treatment of retinal disease
seeking an additional opinion regarding possible preventive
treatment for their fellow, normally sighted eyes. They
related that they were again advised to have no laser pro-
phylaxis, but to return promptly for treatment if and when
they developed RRD in the fellow eye. They had come to
our clinic at the suggestion of a fth retina specialist.
Examination
In addition to rst eye RRD, features of the Stickler ocular
phenotype present in the fellow eyes of the two men
included high myopia from birth, optically clear central
vitreous, cortical vitreous gel opacities, and lattice retinal
degeneration. The father was bilaterally pseudophakic
resulting from early-onset cataracts. The father and son
had pseudophakic visual acuities of 8/200 and 20/125 in
their post RRD eyes, respectively, with visual elds
reduced to an average of 27 degrees in each meridian
(Figure 2A and B, Figure 3A and B).
A full discussion ensued using diagrams and illustra-
tions of vitreous traction, retinal tears, lattice degeneration,
and RRD. A specic form of encircling laser treatment of
the peripheral retina in Stickler syndrome (OSC/SS) was
described as a possible preventive treatment for their fel-
low eyes. Included in the discussion were the rationale and
the risks of treatment, and the fact that there existed no
A B
Figure 2 (A) Final appearance of the father’s right eye fundus after repair of recurrent RRD/PVR in multiple procedures. Postoperative visual acuity is 8/200. Multiple
causative tears with aberrant vitreous traction were noted at RRD repair. (B) Visual eld of the right eye postoperatively.
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prospective clinical trials of this or any other prophylactic
procedure.
15
The alternatives described were focal retinopexy lim-
ited to visible lattice;
15
encircling scleral buckling (more
invasive, and itself not proven);
16
encircling cryopexy
(performed primarily at Cambridge);
9,17
or continued
observation, accepting the natural course of Stickler
syndrome.
9
Treatment
Both the father and the presenting son chose OSC/SS
prophylaxis for their fellow eye, gave written informed
consent prior to each treatment, and were treated with
laser delivery via the indirect ophthalmoscope (IDO)
under laryngeal mask general anesthesia (LMA) without
complications (Figure 4A and B).
The 26-year-old daughter was subsequently examined,
with similar ndings consistent with Stickler phenotype,
including myopia of 20 diopters, 3.75 diopters of astigma-
tism, an optically clear vitreous with “stringy” opacities in
the cortical vitreous gel, and lattice retinal degeneration.
She had modest focal laser prophylaxis to lattice OU. Her
corrected visual acuity was 20/25 right eye and 20/30 left
eye. She was offered OSC/SS in each eye for her
consideration.
While contemplating possible treatment, 6 weeks later
she suffered RRD from a six clock hour GRT in the left
eye that was reattached in her hometown using silicone oil.
Even after silicone oil removal and cataract extraction,
maculopathy limited her nal corrected visual acuity to
20/125 in the left eye and visual eld was reduced to an
average of 32 degrees in each meridian. She then chose
OSC/SS prophylaxis in her fellow right eye and was
treated under LMA in two sessions after written informed
consent.
A 28-year-old son was found to have eight diopters of
myopia, early onset cataracts, abnormally clear central
vitreous, cortical vitreous opacities, and lattice retinal
degeneration. He had minimal laser treatment to areas of
thin retina in both eyes. He chose OSC/SS prophylaxis,
gave written informed consent, and was treated OU under
LMA over a period of 4 years on a schedule of his choice.
He then had successful cataract extraction in his right eye.
After subsequent symptomatic posterior vitreous detach-
ment in the left eye 2 years after nal OSC/SS treatment,
he gave written informed consent and underwent left eye
combined cataract extraction and 27-gauge vitrectomy
with removal of symptomatic vitreous veil opacities.
The father, his three affected children, and a 4-year-old
grandson were each tested for mutations in the genes
known to be involved in Stickler syndrome. No family
A B
Figure 3 (A) Final appearance of the son’s left eye after repair of recurrent RRD/PVR. Postoperative visual acuity is 20/125. Initial RRD was from multiple small defects with
lattice. (B) Visual eld of the left eye postoperatively.
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member was noted to have skeletal abnormalities.
A hearing test was performed on the father.
Results
None of the ve eyes in the four family members treated by
OSC/SS prophylaxis experienced either a retinal tear or an
RRD with an average follow-up of 8.7 years (Video S1).
Each of these ve eyes maintained preoperative corrected
visual acuity of 20/20 to 20/30, with an asymptomatic reduc-
tion of visual eld to an average of 50 degrees in each
meridian post-prophylaxis. The three fellow eyes treated
with OSC/SS have now gone 12, 11, and 8 years after rst
eye RRD without suffering a rhegmatogenous event. The
daughter’s right eye fundus image and visual eld, typical
of the OSC/SS treated eyes, are shown in Figure 5A and B,
respectively.
At vitrectomy performed in the left eye, the eldest son
was noted to have both moderate beading opacities charac-
teristic of STL2 and extensive membranous vitreous veils
(Video S2), distinct however from the anterior membranous
A B
Figure 5 (A) Fundus image of the daughter’s right eye after completed OSC/SS laser prophylaxis. Visual acuity is 20/30 (as preoperatively) corrected with −20.25 +3.75 ×
091. (B) Visual eld of the right eye post OSC/SS.
Figure 4 (A) Step 1 (essential) of OSC/SS. Laser burns of moderately high intensity are placed in a tight grid pattern (one spot width separation) from 2 mm onto the pars
plana to the ora serrata, and approximately 4 mm posteriorly, halfway to the vortex vein ampullae, achieving protection against GRT and anterior defects. Artist Stephen
Gordon. (B) Step 2 (optional) of OSC/SS. Three months after initial treatment, the laser grid is extended posteriorly to and between the vortex vein ampullae, achieving
maximum protection against both GRT and posterior defects throughout the peripheral retina. Used with permission of artist Stephen Gordon, copyright 2020.
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opacity characteristic of STL1 eyes.
3,18
He ultimately
achieved 20/25 uncorrected visual acuity in the right eye
and 20/30 uncorrected near visual acuity in the left eye.
Of the ve OSC/SS-treated eyes, one developed pupil-
lary mydriasis that was moderately symptomatic and per-
sisted for 6 months, but ultimately resolved. No eye
developed epimacular proliferation, vitreous traction exa-
cerbated by treatment, or any other complication.
Each affected family member was found to have an
identical “variant of unknown signicance” mutation in the
gene that is associated with STL2 (Col11A1), less common
than STL1, but having similar RRD propensity.
19
The father
had moderate sensorineural hearing loss. The father and four
of his ve affected siblings/children suffered RRD (5/6,
83%). The one affected child not developing RRD had
received OSC/SS prophylaxis OU, with 7-year follow-up
in the right eye and 3-year follow-up in the left eye.
Discussion
The Stickler Problem
The fundamental problem in Stickler eyes is that the vitr-
eous cavity is only partially lled with gel vitreous from
birth.
5
The central vitreous does not “liquify” - it never
forms. And aqueous uid is ready to breach any retinal
hole or tear that develops. Cortical vitreous movements
and contraction (Video S3) can give rise to tractional
retinal tears, completely independently of posterior vitr-
eous detachment, at an age when normal eyes with
a completely gel-lled vitreous cavity are impervious to
such an occurrence.
5
In fact, less than half of Stickler
RRDs have posterior vitreous detachment (Video S3).
14
Moreover, the vitreous gel that is present adheres to the
retina in a grossly anomalous and unpredictable fashion.
Finally, lattice and perivascular retinal degeneration and
strong foci of vitreous adherence can extend quite poster-
iorly (Figure 6).
4,18
As a consequence of these vitreoretinal abnormalities,
and in the absence of prophylaxis, most STL1 (and prob-
ably STL2, as in this family)
19
Stickler patients experience
RRD, half by age 20, with an 80% probability of fellow
eye RRD within a median of 4 years in the largest obser-
vational report to date.
9
Two of three affected children in
the current family had rst eye RRD by age 26, and one of
three detachments in this family was from GRT. Yet three
fellow eyes treated by OSC/SS laser retinopexy have gone
12 years, 11 years, and 8 years after rst eye detachment
without developing RRD.
Prevention of RRD by adoption of the Cambridge
cryopexy protocol has been hindered by the fact that
cryopexy is now used very sparingly by most retina
specialists, who regard laser retinopexy as superior,
and who have never in their careers performed encir-
cling cryopexy.
18,21
Focal cryopexy and laser retinopexy
are each successful prophylaxis in the hands of surgeons
adept at them. However, the majority of current practi-
tioners are insufciently skilled and reluctant to perform
encirclement with cryopexy, when the laser retinopexy
they expertly perform almost daily is available as
a reasonable encircling prophylaxis alternative.
18
Figure 7 Fundus image of a giant retinal tear (GRT) extending from 9 to 5 o’clock
in the left eye. GRT is most commonly seen in childhood retinal detachments of
Stickler syndrome patients.
Figure 6 Fundus image of pigmented perivascular retinal degeneration extending
radially and posteriorly, as seen in some Stickler syndrome pedigrees.
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OSC/SS Technique
In our experience, Stickler RRD emanating from either
GRT (Figure 7; one of three detachments in this family) or
from multiple posterior tears (Figure 8A and B; Video S3;
two of three detachments in this family) can be reliably
prevented by IDO delivery of a dense grid of laser retino-
pexy starting 2 mm anterior to the ora, extending to and
between the vortex vein ampullae posteriorly. OSC/SS
employs slightly higher power and a tighter grid pattern
(one spot width separation) than in standard OSC, as illu-
strated in Figure 4A and B.
This two-step prophylaxis emulates the successful
Cambridge GRT prophylaxis in Step 1. But in Step 2, it
also attempts to prevent the 9% Cambridge failure rate
over 5.6 years of follow-up, due predominately to new
posterior tears.
9
Step 2 further safeguards treated eyes for
a life expectancy averaging decades beyond the mean age
at which Cambridge cryopexy was performed (14.5 years
bilateral prophylaxis; 22.9 years unilateral prophylaxis).
Treatment of one or both eyes of young, inherently
high-risk Stickler patients is best performed in the operat-
ing room under laryngeal mask general anesthesia (LMA).
In an initial treatment session (Step 1), laser grid treatment
is placed from 2 mm anterior to the ora serrata (reaching
the anterior vitreous base) to 4 mm posterior to the ora
(posterior to the normal vitreous base at 3 mm from the
ora), about halfway to the vortex vein ampullae, taking
care to spare the long posterior ciliary nerves at the three
and nine o’clock meridians (Figure 4A). Step 1 is the
essential step in achieving security for central vision,
with additional steps as described below to be elected by
each patient after further counseling, so as to achieve the
patient’s maximum desired prophylaxis.
After a normal recovery from Step 1 laser retinopexy,
without anterior segment sequelae,
22
(or as a supplement
to Cambridge cryopexy encirclement) a laser treatment
session 3 months later (Step 2) lls in skip areas and
extends further posteriorly to and between carefully loca-
lized vortex vein ampullae. No treatment is applied
directly overlying visible vortex vein ampullae or their
posterior choroidal drainage vessels. Once sufcient
experience accumulates to assure safety and effectiveness,
it may be possible to offer a trial of OSC/SS in a single
treatment.
Total OSC/SS treatment is approximately 2000 to 2400
spots (Figure 4B). If a shallow fornix limits the scleral
depression needed to achieve adequate posterior coverage,
an access conjunctival incision can be used. Alternatively,
the posterior extent of treatment can be incrementally
adjusted using a wide-angle contact lens and a slit lamp
in the clinic during a nal session with topical anesthesia.
Beyond accurate grid laser placement, good control of
laser power is critically important. The delicate
Figure 8 (A) Intraoperative image of seven post equatorial retinal tears extending from 8 to 10 o’clock temporally along a prominent circumferential line of vitreous
traction, causing total RRD in the right eye of a 14-year-old female with STL1, congenital extreme myopia (26 diopters), and abnormal vitreous (Video S3). These tears
occurred well posterior to standard OSC prophylaxis performed 4 months previously. (B) Postoperative image of the same retina reattached under silicone oil, with
corrected visual acuity in the eye of 20/30. Note the prominent line of vitreous traction from 5 to 11 o’clock that could not be safely removed during the initial repair
despite retinal stabilization with peruorocarbon liquid. Laser retinopexy extends quite posteriorly to encompass all tears and the traction line that was further reduced
upon silicone oil removal.
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neurosensory retina can develop necrotic defects when the
chorioretinal complex is treated with excessive power
density or overlapping burns, weakening the retina instead
of strengthening it as intended. The denition of “burn” is
“to alter or destroy by the action of heat.”
23
The distinction
between altering to produce a strengthening adhesion, and
destroying by causing retinal necrosis can be minimal,
requiring vigilance in monitoring grid placement, power
density and the resultant retinal “whitening.”
Posterior Prophylaxis Uncertainty
Optimal prophylaxis in SS must extend more posteriorly
than in non-syndromic eyes because both retinal degenera-
tion and anomalous vitreous traction commonly extend
more posteriorly.
20
But any encircling laser retinopexy
reduces the peripheral visual eld while increasing central
vision security, and this trade-off increases in OSC/SS
prophylaxis as the retinopexy border is extended more
posteriorly. Potentially greater loss of visual eld under-
standably gives rise to controversy. Yet even after Step 2
of OSC/SS retinopexy, the loss of peripheral eld was
asymptomatic in all four treated members of this family
and rated as a 0% disability by Estermann scoring.
24
In a 2019 review, Coussa et al noted that encircling
prophylaxis is commonly performed in fellow eyes when
an initial Stickler RRD is repaired, but that the optimal
posterior extent of treatment has not been established.
25
While posterior tears causing retinal detachment are rela-
tively rare in non-syndromic eyes, in a series of Stickler
detachments, Billington et al noted multiple small tears
with “many post equatorial and at different distances from
the ora serrata.”
26
In 1968, just 3 years after Gunnar Stickler’s rst report,
Hagler reported on 33 patients with familial radial perivas-
cular retinal degeneration (Figure 6) and ocular features that
have subsequently been shown to characterize SS, including
22 retinal detachments.
20
None were caused by GRT, but
three related family members suffered GRT detachments.
Hagler reported a 36% failure rate in detachment repair due
to multiple posterior tears and thus referred to these as
“malignant” detachments. In 2002, Parma et al showed that
this same pedigree was indeed genetically STL1. RRD
occurred in 65% of 100 patients, with half bilaterally, and
70% of detachments occurred by age 18.
4
In a total of four literature reports specically analyzing
Stickler RRD, approximately 82 of 158 eyes (52%) had
multiple small tears, while 43 eyes (27%) had giant retinal
tears.
10,14,26,27
Based on these reports and an estimated
lifetime RRD risk in SS patients of over 65%,
4,17
one
would expect at least a 30% remaining risk of RRD from
posterior tears in SS patients even after GRT prophylaxis.
Thus, posterior prophylaxis via Step 2 OSC/SS laser reti-
nopexy can reasonably be offered to all STL1 and STL2
patients. The Cambridge operative experience with over
250 Stickler detachments might considerably enhance our
knowledge of causative tear locations, further dening the
posterior prophylaxis (beyond GRT prophylaxis at the ora)
needed to optimally secure central vision for a lifetime.
9
The extent of laser retinopexy preventive treatment and
placement of the posterior border of prophylaxis in
Stickler eyes are ultimately decisions to be made in each
eye based on each physician’s judgment and each patient’s
preference (Supplemental Report). For the three family
members who lost vision due to RRD in one eye, choosing
maximum retinopexy prophylaxis by both Step 1 and Step
2 OSC/SS was an easier decision. Similarly, other Stickler
patients with one eye detachment or with a multi-
generational family history of detachment would likely
be so inclined.
Vitrectomy as Prophylaxis
It is indisputable that STL1 and STL2 patients are at
extreme risk for RRD, and that tractional tears account for
the preponderance of these detachments.
9,10,14,17–19,25–27
Consequently, 27-gauge vitrectomy to prevent vitreous
traction (carrying less than a 1% risk in our experience,
when performed with specic precautions) is now
a reasonable, nal preventive option (Step 3) to be consid-
ered in selected eyes after completion of OSC/SS retino-
pexy. Substantial advances in ultra-high-speed vitrectomy
probes, low-end suction control, Kenalog vitreous staining,
and wide-eld microscopes have nally made Step 3
a reasonably safe alternative to complete reliance on pro-
phylactic retinopexy. This nal step helps SS eyes avoid
a lifetime of vitreous tractional events that are more com-
mon but less predictable (as to location) in Stickler eyes
than in non-syndromic eyes. As an example, the seven tears
seen in the Stickler RRD of Video S3 were so posterior that
they likely would not have been prevented even by the
maximum OSC/SS retinopexy prophylaxis here described.
Alsharani et al found that vitreous veils were present at
the site of tears in 70 consecutive Stickler detachments.
14
Such opacities (Figure 9) may help guide vitreous removal
as a nal prophylactic measure in some Stickler eyes, as in
the vitrectomy performed in the older son of this family
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26
Morris et al Dovepress

(Video S2). Moreover, Stickler patients who present with
symptomatic vitreous opacities may be at especially high
risk of detachment. In fact, all Stickler patients and their
parents should be well educated to promptly report pre-
monitory signs of vitreous traction for professional
assessment.
Conclusion
A recent comprehensive analysis of Stickler syndrome
RRD prophylaxis by the National Institute for Health
Research of the United Kingdom concluded that
a prospective, randomized trial of prophylaxis in this rare
disease was impractical and instead recommended
a nonrandomized, prospective, cohort comparison study
of ongoing individual efforts.
28
We hope that dissemina-
tion of the OSC/SS technique will be another signicant
step, building on the pioneering work of the Cambridge
group, towards the goal of developing an effective, statis-
tically validated prophylaxis for RRD in Stickler
syndrome.
OSC/SS is a noninvasive treatment whose sole purpose
is risk reduction, and the risk of treatment itself has been
minimal when applied appropriately.
12,13,18
However, each
physician should remain mindful that such treatment is
tantamount to a permanent laser signature and to always
“laser” as much as necessary but as little as possible, with
great care betting the permanent changes inevitably
attending such retinopexy.
Encircling prophylaxis is a reasonable option for
Stickler patients to consider. And yet after undergoing
ve retinal detachment repairs with nal profound visual
loss in three family members, and after being seen by four
retinal specialists over a period of years, none of the four
affected family members had learned of either the widely
used encircling laser prophylaxis option,
12,13,29–36
or the
Cambridge encircling cryopexy prophylaxis for their fel-
low eyes. Even in the absence of level-one evidence of
effectiveness,
15
we must provide Stickler patients with all
the information we have, enabling them to make their own
fully informed prophylaxis choice. For in the absence of
effective RRD prevention they spend each day “under the
sword of Damocles,” with the eminent and ever-present
danger of sudden blindness.
37
Data Sharing Statement
Additional material related to this article can be found at
www.helenkellerfoundation.org.
Ethics and Consent Statement
This retrospective case series study was determined to be
exempt from IRB approval by the Western Institutional
Review Board and was conducted in accordance with the
tenets of the Declaration of Helsinki for research involving
human subjects. Patients provided written informed con-
sent for their case details to be published.
Acknowledgments
As in many prior articles, the authors are grateful for
excellent research, clinical, and clerical support by
Christina Sullivan, Jessica Haynes, Dewayne Conn, and
Laura Beckwith. C. Diane Scharper has again provided
expert editing services. The authors also appreciate the
supportive environment provided by the staff and physi-
cians of Retina Specialists of Alabama and the UAB
Callahan Eye Hospital.
Author Contributions
Dr. Robert Morris initally conceptualized OSC/SS, per-
formed all treatments, and wrote the rst draft. All addi-
tional authors made substantial contributions to conception
and design, acquisition of data, or analysis and
Figure 9 Intraoperative image of vitreous veils in the left eye of the elder son,
an STL2 patient (Video S2).
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27
Dovepress Morris et al

interpretation of data; took part in drafting the article or
revising it critically for important intellectual content;
agreed to submit to the current journal; gave nal approval
of the version to be published; and agree to be accountable
for all aspects of the work.
Funding
Partial funding was provided by the Helen Keller
Foundation for Research and Education, through grants
by the Hanna Charitable Trust and the Kent Companies,
and by Retina Specialists of Alabama LLC.
Disclosure
The authors report no conicts of interest in this work
nancial or otherwise.
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