Association between laser flare photometry and symptom duration in primary rhegmatogenous retinal detachment

Abstract

Purpose
The purpose of this study was to investigate preoperative blood-ocular barrier disruption via laser flare photometry (LFP) in patients diagnosed with rhegmatogenous retinal detachment (RRD), and to analyse possible associations with symptom duration and anatomical parameters.

Methods
We retrospectively analysed consecutive patients presenting with RRD at a single centre between January 2016 and March 2020. LFP was performed in both eyes after pupillary dilatation prior to RRD surgery. Symptom duration, extent of retinal detachment, and lens status were assessed. For statistical analysis, we carried out the unequal variances t test and Welch’s analysis of variance (ANOVA).

Results
We included 373 eyes of 373 patients (mean age 63.96 years ± 10.29; female:male ratio 1:1.8). LFP values quantified in photon count per millisecond (pc/ms) increased with longer symptom duration when comparing patients with a symptom duration of 0–3 days ( n = 158; 9.25 ± 6.21 pc/ms) and ≥ 4 days ( n = 215; 11.97 ± 11.58 pc/ms; p = 0.004). LFP values also rose with the number of retinal quadrants affected by RRD (1 quadrant, 6.82 ± 4.08 pc/ms; 2 quadrants, 10.08 ± 7.28 pc/ms; 3 quadrants, 12.79 ± 7.9 pc/ms; 4 quadrants, 31.57 ± 21.27 pc/ms; p < 0.001), macula off status (macula on, 8.89 ± 6.75 pc/ms; macula off, 12.65 ± 11.66 pc/ms; p < 0.001), and pseudophakic lens status (pseudophakia, 12.86 ± 9.52 pc/ms; phakia: 9.31 ± 9.67 pc/ms; p < 0.001).

Conclusion
In RRD patients, blood-ocular barrier disruption quantified by LFP is associated with the duration of symptoms and the disease’s anatomical extent. These results warrant further investigation of the potential clinical use of LFP in RRD.

Full text

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https://doi.org/10.1007/s10792-022-02532-x
ORIGINAL PAPER
Association betweenlaser flare photometry andsymptom
duration inprimary rhegmatogenous retinal detachment
LeonieMenghesha · VerenaSchoeneberger·
StefanieGerlach· JuliaLemke· TimU.Krohne·
NicolasFeltgen· FriederikeSchaub
Received: 20 December 2021 / Accepted: 11 September 2022 / Published online: 5 October 2022
© The Author(s) 2022
we carried out the unequal variances t test and Welch’s
analysis of variance (ANOVA).
Results We included 373 eyes of 373 patients (mean
age 63.96 years ± 10.29; female:male ratio 1:1.8).
LFP values quantified in photon count per millisec-
ond (pc/ms) increased with longer symptom duration
when comparing patients with a symptom duration
of 0–3days (n = 158; 9.25 ± 6.21 pc/ms) and ≥ 4days
(n = 215; 11.97 ± 11.58pc/ms; p = 0.004). LFP values
also rose with the number of retinal quadrants affected
by RRD (1 quadrant, 6.82 ± 4.08pc/ms; 2 quadrants,
10.08 ± 7.28 pc/ms; 3 quadrants, 12.79 ± 7.9 pc/ms;
4 quadrants, 31.57 ± 21.27 pc/ms; p < 0.001), macula
off status (macula on, 8.89 ± 6.75pc/ms; macula off,
12.65 ± 11.66 pc/ms; p < 0.001), and pseudophakic
lens status (pseudophakia, 12.86 ± 9.52 pc/ms; pha-
kia: 9.31 ± 9.67pc/ms; p < 0.001).
Conclusion In RRD patients, blood-ocular barrier
disruption quantified by LFP is associated with the
duration of symptoms and the disease’s anatomical
extent. These results warrant further investigation of
the potential clinical use of LFP in RRD.
Keywords Rhegmatogenous retinal detachment·
Laser flare photometry· Blood-ocular barrier disruption
Introduction
A disruption in the blood-ocular barrier occurs in
response to intraocular inflammation. Slit lamp
Abstract
Purpose The purpose of this study was to investigate
preoperative blood-ocular barrier disruption via laser
flare photometry (LFP) in patients diagnosed with
rhegmatogenous retinal detachment (RRD), and to
analyse possible associations with symptom duration
and anatomical parameters.
Methods We retrospectively analysed consecutive
patients presenting with RRD at a single centre between
January 2016 and March 2020. LFP was performed in
both eyes after pupillary dilatation prior to RRD sur-
gery. Symptom duration, extent of retinal detachment,
and lens status were assessed. For statistical analysis,
Nicolas Feltgen and Friederike Schaub contributed equally
as co-senior authors.
This material is original research, has not been previously
published, and has not been submitted for publication
elsewhere while under consideration.
L.Menghesha(*)· V.Schoeneberger· S.Gerlach·
J.Lemke· T.U.Krohne· F.Schaub
Department ofOphthalmology, Faculty ofMedicine
andUniversity Hospital Cologne, University ofCologne,
Kerpener Strasse 62, 50937Cologne, Germany
e-mail: leonie.menghesha@uk-koeln.de
V.Schoeneberger· F.Schaub
Department ofOphthalmology, University Medical Center
Rostock, University ofRostock, Rostock, Germany
N.Feltgen
Department ofOphthalmology, University Hospital
Goettingen, Goettingen, Germany
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bio-microscopy is traditionally applied to evaluate an
increase in protein in the eye’s anterior chamber, which
produces an optical phenomenon called the Tyndall
effect, or flare. Laser flare photometry (LFP) already
qualifies as an objective quantitative method to non-
invasively measure protein particles in the anterior
chamber in the photon count per millisecond (pc/ms).
Until now, few studies have investigated LFP val-
ues in patients with rhegmatogenous retinal detach-
ment. Hoshi etal. [4] evaluated aqueous flare levels
with LFP in eyes with RRD over time after vitrec-
tomy, whereas Chalam et al. [1] investigated them
subjectively via slit lamp bio-microscopy. Further-
more, studies by Hoerster etal. and Schroeder et al.
demonstrated that laser flare levels before surgery
are a predictor when assessing the risk for prolifera-
tive vitreoretinopathy (PVR) associated with elevated
re-detachment rates in eyes suffering primary RRD
[3, 12]. A prospective study by Mulder et al. failed
to validate these findings in an independent prospec-
tive study. Yet LFP values seem to have a predictive
value regarding the postoperative PVR risk. As a
consequence, the value of preoperative laser flare val-
ues as a predictor for PVR remains unclear [10, 11].
The complex problem of PVR development and the
associated rate of retinal re-detachment after primary
surgical success is currently the subject of intensive
research efforts with the aim to find preventive and
therapeutic options. In relation to this problem, the
search for influencing factors is also being pursued.
So far, to the best of our knowledge, there is
no data describing possible associations between
anatomical parameters and symptom duration in
eyes with RRD and laser flare values. Therefore,
the aim of the present study was to complement
previous knowledge by assessing, for the first time, an
association between preoperative blood-ocular barrier
disruption measured via LFP in terms of symptom
duration and anatomic extent in patients with RRD.
Methods
This single-centre retrospective study relied on data
acquired at the Department of Ophthalmology, Uni-
versity Hospital of Cologne, Germany between 27th
January 2016 and 12th March 2020. It was approved
by the Ethics Committee of the University of Cologne
(20-1043). All tenets of the declaration of Helsinki
have been followed.
Collection of clinical data, inclusion, and exclusion
criteria
Medical records of 538 consecutive patients (mean
age 64 ± 10.3 years) with RRD were reviewed. Epi-
demiological data (age, gender) and symptom dura-
tion (period in days from first recognised symptoms
to the day the laser flare value was measured) were
taken from the patient file. Ophthalmological exami-
nations included best spectacle-corrected visual acu-
ity (BSCVA) and slit lamp bio-microscopy as well as
fundoscopy of both eyes in medical mydriasis with
0.5% tropicamide or 5% phenylephrine hydrochloride.
The extent of RRD including affected retinal quadrants
(1–4), macular attachment status (macula on, macula
off) based on the fundus examination and fundus draw-
ings on the admission day, and lens status (phakia,
pseudophakia) were documented. The charts of the
patients were reviewed for previous intraocular surger-
ies and concomitant diseases. Our exclusion criteria
were inaccurate laser flare values with standard devia-
tion (SD) of LFP values higher than 15pc/ms (n = 13),
unknown symptom duration (n = 20), missing preop-
erative flare measurements (n = 57), diabetic macular
oedema (n = 1), secondary RD including visible prolif-
erative vitreoretinopathy (n = 53), history of refractive
surgery of the cornea (n = 11), cystoid macular oedema
(n = 1), cornea guttata (n = 5), active or inactive uvei-
tis (n = 2), proliferative diabetic retinopathy (n = 1) and
synchisis scintillas (n = 1). No eyes with a history of
trauma were included. Thus, a total of 165 patients had
to be excluded, and 373 qualified for further analysis.
Laser flare photometry (LFP)
Preoperative LFP of both eyes was performed in
medical mydriasis on the day of admission to the
department with the Kowa FM-500 Laser Flare-Cell
Meter (Kowa Company Ltd, Tokyo, Japan—distribu-
tor: Kowa Optimed Deutschland GmbH, Düsseldorf,
Germany) to measure the laser flare value in both
eyes’ anterior chambers taking at least seven meas-
urements. After excluding the highest and lowest
laser flare levels, the average and SD were calculated.
To avoid external scattering, the room was darkened
during measurements. LFP was performed prior to
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Goldman three mirror contact lens examination and
Goldman applanation tonometry.
Statistical analyses
Descriptive data were collected and analysed by SPSS
(version 25.0 for windows; SPSS, Inc., Chicago,
IL). The BSCVA was converted to the logarithm
of Minimum Angle of Resolution (logMAR). The
following groups were classified according to
symptom duration: group 1: 0–3days (n = 158), group
2: ≥ 4 days (n = 215), group 2a: 4–7 days (n = 154),
and group 2b: > 7days (n = 61). Depending on normal
distribution of the interval-scaled parameters we had
analysed, we conducted the unequal variances t test
and Welch’s analysis of variance (ANOVA) including
Games-Howell post hoc analysis and multiple linear
regression for statistical analysis. We observed no
homogeneity of variance (Levene’s test, p < 0.001).
The level of significance was defined as p < 0.05.
Results
Totally 373 eyes with primary RRD were included
(right eye n = 201, left eye n = 172) of 373 patients
(mean age 63.96 years ± 10.29; female:male ratio
1:1.8). The distribution of documented patient charac-
teristics and laser flare values is illustrated in Table1.
In patients from whom we had LFP measurements in
both eyes (n = 356), the mean LFP values were higher
(10.98 pc/ms ± 9.94) than in the unaffected fellow
eyes (6.68 pc/ms ± 4.53; p < 0.001, paired t test). A
normal healthy eye shows values between 1 and 9pc/
ms. There were no significant differences in laser flare
values between men and women. We noted that laser
flare values rose significantly in conjunction with
macula-off status, in patients with pseudophakia, and
with the number of quadrants affected. There was no
homogeneity of variance (Levene’s test, p < 0.001).
Therefore, Welch’s ANOVA was assessed to analyse
the extent of RRD (Welch’s F (3, 72.22) = 21.94,
p < 0.001) (Table1).
Of 373 eyes with RRD, we classified two main
groups and two subgroups based on symptom dura-
tion. Laser flare values increased significantly with
longer symptom duration in groups 1 and 2, as well
as in subgroup analysis of group 1 and subgroup 2a
(Table2, Fig.1).
In eyes presenting macula-off status, laser flare
value rose significantly the longer the patients’
symptoms lasted, but not in eyes with macula-on
status. In the subgroups of eyes with 1, 2, 3 or 4
quadrants affected, we identified no significant
difference in laser flare values depending on symptom
duration. In phakic eyes, laser flare values were
significantly higher with longer symptom duration,
but not in pseudophakic eyes. (Table3)
We conducted a one-way analysis of variance
(ANOVA) for 373 eyes to assess a difference in LFP
values among different groups in symptom-dura-
tion terms (group 1 n = 158, subgroup a n = 154 and
Table 1 Epidemiological
data and anatomical details
on patient cohort
Unequal variances t
test (sex, macula status,
lens status) and Welch’s
ANOVA (extent of RRD)
Epidemiological data Frequency
(percentage %)
Laser flare level
(mean ± SD in pc/ms)
p value 95% Confidence
interval (CI)
Sex 0.435 [−1.28, 2.96]
Male
Female
241 (64.6)
132 (35.4)
11.11 (± 9.5)
10.27 (± 10.16)
Macula status < 0.001 [−5.7, −1.83]
On
Off
182 (48.8)
191 (51.2)
8.9 (± 6.8)
12.7 (± 11.7)
Extent of RD < 0.001 [9.82, 11.80]
1 quadrant
2 quadrants
3 quadrants
4 quadrants
100 (26.8)
197 (52.8)
55 (14.7)
21 (5.6)
6.82 (± 4.08)
10.08 (± 7.28)
12.79 (± 7.9)
31.57 (± 21.27)
Lens status < 0.001 [−5.52, −1.57]
Phakia
Pseudophakia
215 (57.6)
158 (42.4)
9.31 (± 9.67)
12.86 (± 9.52)
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subgroup b n = 61). As there was no homogeneity of
variance (Levene’s test, p < 0.001) Welch’s ANOVA
was performed. We observed a significant differ-
ence in LFP values among symptom-duration groups
(Welch’s F (2, 141.36) = 4.23, p = 0.016). Games-
Howell post hoc analysis revealed a significant differ-
ence between LFP values in group 1 (0–3days) and
subgroup a (≥ 4–7 days) (p < 0.029, MDiff = − 2.7,
95%-CI [−5.17, −0.22]).
Multiple linear regression was conducted to deter-
mine the relative contribution of each independent
variable. We included a total of 367 eyes in multiple
linear regression to determine the relative contribu-
tion of independent variables. We excluded 6 eyes
with studentized deleted residuals (SDR) over 3. The
model had no autocorrelation as the value of the Dur-
bin-Watson statistic was 1.5. The R2 for the overall
model was 0.26 (adjusted R2 = 0.25). Lens status
(p < 0.001) and extent of RD (p < 0.001) were statisti-
cally significant coefficients.
Discussion
Since there seem to be numerous factors influencing
LFP, a comprehensive scientific analysis of possible
associations is desirable. Few studies have investigated
LFP in eyes with RRD [3, 4, 10–12], and to date no
data has been published describing the potential asso-
ciations between laser flare values, anatomical details,
and symptom duration in RRD. We investigated these
characteristics to enhance existing knowledge and as
experience has shown that they are often associated
Table 2 Distribution in
groups and subgroups.
Association with laser flare
values
Unequal variances t test
Symptom duration Frequency
(percentage %)
Laser flare value
(mean ± SD) in pc/ms
p value 95% Confidence
interval (CI)
Group 1: 0–3days 158 (42.4) 9.25 (± 6.21) 0.004 [−4.56, −0.89]
Group 2: ≥ 4days 215 (57.6) 11.97 (± 11.58)
Subgroup a: ≥ 4–7days 154 (41.3) 11.94 (± 11.5) 0.97 [−3.6, 3.49]
Subgroup b: > 7days 61 (16.4) 12.02 (± 11.86)
Subgroup analysis
Group 1: 0–3days 158 (42.4) 9.25 (± 6.21) 0.011 [−4.77, −0.63]
Subgroup a: ≥ 4–7days 154 (41.3) 11.94 (± 11.5)
Group1: 0–3days 158 (42.4) 9.25 (± 6.21) 0.087 [−5.96, 0.41]
Subgroup b: > 7days 61 (16.4) 12.02 (± 11.86)
Fig. 1 Boxplots for
LFP values in pc/ms for
symptom duration group
1 (n = 158) and group 2
(n = 215), p = 0.004. Boxes
represent first quartile,
median (solid lines), mean
(dashed lines) and third
quartile values; whiskers
represent extreme values
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with each other in everyday clinical practice in the
care of patients with retinal detachment.
In the current study, we found that a longer symp-
tom duration in eyes with primary RRD in the first
week leads to an increase in laser flare values poten-
tially because of the persisting disruption in the
blood-ocular barrier [7]. This is supported by the fact
that eyes with longer-lasting RRD and higher laser
flare values reveal greater inflammation and infiltra-
tion by activated macrophages over time. Together
with the neurosensory retina’s being separated from
the retinal pigment epithelium, this is associated with
changes in cytokine and chemokine levels [2, 5, 6,
13].
Furthermore, there seems to be a relationship
between anatomical features in case of RRD, such
as the macula attachment status and quadrant num-
bers affected by the RRD. We demonstrate that
these characteristics are also associated (in terms
of their extent) with significantly higher laser flare
values. Moreover, in eyes with advanced RRD
(macula off, 4 affected quadrants) we noted a sig-
nificant association with aqueous flare intensity and
longer symptom duration. These results confirm the
analyses from previous studies and appear reason-
able in the light of the previously described clinical
understanding of blood-ocular barrier disruption in
patients with retinal detachment.
Interestingly, pseudophakic eyes revealed higher
laser flare values than phakic eyes. However, as
mentioned before in phakic eyes, laser flare val-
ues were significantly higher with longer symptom
duration, but not in pseudophakic eyes. A possible
cause of increased readings in pseudophakia could
be an increased flare due to recent cataract sur-
gery. Unfortunately, prior surgeries are often per-
formed outside of our clinic in an outpatient setting
and complete data regarding the exact time inter-
val between other procedures such as cataract sur-
gery are not always available. In addition, it must
be considered that in pseudophakia there might be
an increased flow of protein from the vitreous cav-
ity into the anterior chamber of the eye. In previ-
ous studies, Miyake’s analyses using vitreous fluo-
rophotometry indicated that blood-ocular barrier
disruption was related to surgical method (intraca-
psular cataract extraction and extracapsular cataract
extraction) and age. Furthermore, a longer duration
of the barrier disturbance than initially suspected
was observed [8, 9]. Further research and analysis
on this phenomenon are already underway in a com-
plementary study (unpublished data).
Table 3 Association between laser flare values and anatomical details regarding symptom duration
Unequal variances t test
Macula status (frequency) Group (frequency) Laser flare value
(mean ± SD) in pc/ms
p value 95% Confidence interval
On
On
Group 1: 0–3days (n = 78)
Group 2: ≥ 4days (n = 80)
8.06 (± 4.74)
9.51(± 7.9)
0.124 [−3.32, 0.4]
Off
Off
Group 1: 0–3days (n = 104)
Group 2: ≥ 4days (n = 111)
10.41 (± 7.21)
14.27 (± 13.83)
0.013 [−6.9, −0.82]
Extent of RD
1 quadrant Group 1: 0–3days (n = 47)
Group 2: ≥ 4days (n = 53)
6.65 (± 3.87)
6.97 (± 4.3)
0.695 [−1.94, 1.3]
2 quadrants Group 1: 0–3days (n = 89)
Group 2: ≥ 4days (n = 108)
9.93 (± 6.7)
10.2 (± 7.5)
0.798 [−2.3, 1.77]
3 quadrants Group 1: 0–3days (n = 19)
Group 2: ≥ 4days (n = 36)
10.92 (± 5.77)
13.77 (± 8.73)
0.154 [−6.8, 1.1]
4 quadrants Group 1: 0–3days (n = 3)
Group 2: ≥ 4days (n = 18)
18.93 (± 7.75)
33.68 (± 22.19)
0.06 −30.27, 0.78]
Lens status
Phakia Group 1: 0–3days (n = 82)
Group 2: ≥ 4days (n = 133)
7.26 (± 4.73)
10.57 (± 11.57)
0.004 [−5.54, −1.08]
Pseudophakia Group 1: 0–3days (n = 76)
Group 2: ≥ 4days (n = 82)
11.39 (± 6.9)
14.23 (± 11.3)
0.057 −5.76, 0.08]
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Limitations of the present study are its
retrospective design. We could not report the exact
duration of symptoms in hours or single days for
all patients, so that a detailed association with laser
flare values was not possible, and groups had to be
formed based on symptom durations as recorded in
the patients’ files.
Furthermore, the postsurgical course of laser
flare values in association with anatomical
parameters and symptom durations deserves
further investigation as well. Our data do not yet
allow an investigation of a possible association
between preoperatively measured flare values and
postoperative outcomes including visual acuity
improvement and PVR development, as well
as surgical success. Another limitation for the
investigation of these questions is the size of the
studied collective. A much larger cohort would be
needed to obtain reliable results, so a multicentre,
prospective, randomized study is desirable.
Nevertheless, the presented analyses and new
results contribute to previous knowledge and lead to
a better understanding of the influencing factors of
LFP and blood-ocular barrier disorder. In eyes with
RRD, we report an association between laser flare
values and symptom duration and the anatomical
extent of disease in a large patient cohort for the
first time. Therefore, LFP should be investigated
in further clinical studies in conjunction with
assessing the surgical and functional outcome.
Acknowledgements All submitting authors have full control
of all primary data.
Author’s contribution Conception and design were
contributed by LM, NF, FS. Data collection, evaluation and
analyses, preparation, review, and approval of the manuscript
were contributed by all authors.
Funding Open Access funding enabled and organized by
Projekt DEAL. No funding was received for this research.
Declarations
Conflict of interest German Research Foundation FA 441/4-
1 to F. Schaub. The sponsor had no role in the design or imple-
mentation of this research. All other authors certify that they
have no affiliations with or involvement in any organization or
entity with any financial interest (such as honoraria; educational
grants; participation in speakers’ bureaus; membership, em-
ployment, consultancies, stock ownership, or other equity inter-
est; and expert testimony or patent-licensing arrangements), or
non-financial interest (such as personal or professional relation-
ships, affiliations, knowledge or beliefs) in the subject matter or
materials discussed in this manuscript.
Ethical approval The study was approved by the Ethics Com-
mittee of the University of Cologne (20-1043). All tenets of the
declaration of Helsinki have been followed.
Open Access This article is licensed under a Creative
Commons Attribution 4.0 International License, which permits
use, sharing, adaptation, distribution and reproduction in any
medium or format, as long as you give appropriate credit to the
original author(s) and the source, provide a link to the Creative
Commons licence, and indicate if changes were made. The
images or other third party material in this article are included
in the article’s Creative Commons licence, unless indicated
otherwise in a credit line to the material. If material is not
included in the article’s Creative Commons licence and your
intended use is not permitted by statutory regulation or exceeds
the permitted use, you will need to obtain permission directly
from the copyright holder. To view a copy of this licence, visit
http:// creat iveco mmons. org/ licen ses/ by/4. 0/.
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