Co esponding au ho : Muhammad Asim Saad
Copy igh © 2025 Au ho (s) e ain he copy igh o his a icle. This a icle is published unde he e ms o he C ea i e Commons A ibu ion Liscense 4.0.
Re ac i e e o de ec ion in d y eye disease
Tan ee Ahmed Choudh y 1 and Muhammad Asim Saad 2, *
1 Assis an P o esso Oph halmology, CMH Kha ian Medical College.
2 Bs Public Heal h, Uni e si y o Ka achi.
Wo ld Jou nal o Ad anced Resea ch and Re iews, 2025, 27(02), 1991-1996
Publica ion his o y: Recei ed on 18 July 2025; e ised on 24 Augus 2025; accep ed on 26 Augus 2025
A icle DOI: h ps://doi.o g/10.30574/wja .2025.27.2.3039
Abs ac
Backg ound: D y eye disease (DED) is a p e alen ocula su ace diso de ha can in luence isual pe o mance and
e ac i e measu emen s. Ea ly de ec ion o e ac i e e o s in pa ien s wi h a ying deg ees o DED may acili a e
app op ia e managemen and educe isual mo bidi y.
Objec i e: To e alua e e ac i e e o de ec ion pa e ns in pa ien s wi h di e en se e i ies o d y eye disease.
Me hods: A e ospec i e c oss-sec ional s udy was conduc ed on 50 pa ien s, s a i ied in o h ee g oups: no d yness
(n=16), mild- o-mode a e d yness (n=18), and se e e d yness (n=15). Clinical and biochemical pa ame e s including
age, gende , BMI, blood p essu e, as ing blood suga (FBS), HbA1c, hemoglobin, and choles e ol le els we e compa ed.
S a is ical signi icance was assessed using app op ia e es s, wi h a p- alue <0.05 conside ed signi ican .
Resul s: The mean age was signi ican ly highe in he se e e d yness g oup (59.1 ± 5.2 yea s) compa ed o pa ien s
wi hou d yness (48.2 ± 5.8 yea s, p=0.037). Female gende was mo e p e alen in mild- o-mode a e d yness (24%)
compa ed o se e e d yness (4%) (p<0.001). Highe as ing blood suga (170.5 ± 82.5 mg/dL, p<0.001) and HbA1c
le els (8.3 ± 2.1%, p<0.001) we e obse ed in se e e d yness pa ien s. Hemoglobin le els we e signi ican ly lowe in
mild- o-mode a e and se e e d yness g oups compa ed o hose wi hou d yness (p<0.001). No signi ican di e ences
we e no ed in BMI, sys olic o dias olic blood p essu e, o choles e ol.
Conclusion: Inc easing se e i y o d y eye disease is associa ed wi h olde age, poo glycemic con ol, and lowe
hemoglobin le els, which may in luence e ac i e e o de ec ion. Inco po a ing sys emic me abolic assessmen in
pa ien s wi h DED may imp o e e ac i e accu acy and isual ou comes.
Keywo ds: D y Eye Disease; Re ac i e E o De ec ion; Hba1c; Fas ing Blood Suga ; Hemoglobin; Visual Ou comes;
Ocula Su ace; Re ospec i e C oss-Sec ional S udy
1. In oduc ion
D y eye disease (DED) is a mul i ac o ial diso de o he ocula su ace cha ac e ized by ea - ilm ins abili y,
hype osmola i y, ocula su ace in lamma ion, and neu osenso y abno mali ies, leading o discom o and luc ua ing
isual dis u bance. The TFOS DEWS II epo ede ined DED a ound he cen al concep o ea - ilm homeos asis loss,
emphasizing ha dis up ed ea s comp omise op ical quali y and ision- ela ed unc ion e en in he absence o o e
co neal pa hology (C aig e al., 2017).
Epidemiological s udies es ima e ha app oxima ely 10–20% o adul s o e 40 yea s su e om clinically signi ican
DED, wi h p e alence ising due o aging popula ions, digi al sc een exposu e, en i onmen al ac o s, and sys emic
Wo ld Jou nal o Ad anced Resea ch and Re iews, 2025, 27(02), 1991-1996
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medica ion use (B i en-Jones e al., 2024; Mohamed e al., 2024). These ends ha e made DED one o he mos common
easons o oph halmic consul a ions and an impo an cause o impai ed isual unc ion and educed quali y o li e.
Al hough DED is classically associa ed wi h ocula discom o such as bu ning, g i iness, and o eign-body sensa ion,
i s op ical consequences a e o en o e looked. The p e-co neal ea ilm cons i u es he i s e ac i e su ace o he
eye, and when uns able, i c ea es su ace i egula i y be ween blinks, p oducing highe -o de abe a ions (HOAs),
inc eased ligh sca e , and deg aded modula ion ans e unc ion (Mon és-Micó, 2010). Pa ien s equen ly desc ibe
“ luc ua ing” o “ghos ing” ision, which b ie ly clea s a e blinking, a symp om di ec ly a ibu able o ea - ilm
ins abili y and wa e on luc ua ions (Denoye e al., 2012).
These op ical ins abili ies di ec ly a ec e ac i e e o de ec ion. Objec i e echniques such as au o e ac o s and
wa e on abe ome e s assume a s able co neal su ace, ye in DED, i egula ea dynamics can bias sphe ical and
cylind ical measu emen s, exagge a e as igma ism, and educe ke a ome ic epea abili y (Kusada e al., 2023).
E idence indica es ha HOAs measu ed sho ly a e blinking co ela e wi h ea - ilm b eakup and epi helial disease,
unde sco ing he iming o measu emen s as a de e minan o accu acy (Mon és-Micó, 2010).
De ice-based s udies highligh a iabili y in measu emen eliabili y. Fo ins ance, Scheimp lug imaging sys ems ha e
shown ela i ely obus epea abili y in DED, while Placido-based opog aphy ends o a y mo e, pa icula ly in mild
disease s ages (Doğan e al., 2022). Compa a i e s udies o wa e on and au o e ac o eadings demons a e
signi ican disag eemen wi h subjec i e e ac ion in DED pa ien s, ein o cing ha subjec i e mani es e ac ion
emains he gold s anda d when pe o med wi h blink con ol and ocula -su ace awa eness (Zadnik e al., 2020).
Managemen o DED has also been shown o imp o e e ac i e accu acy. Sho - e m ins illa ion o lub ican s educes
HOAs, s abilizes ke a ome ic eadings, and imp o es he eliabili y o biome ic measu emen s (Kaido e al., 2016).
Clinically, un ea ed DED has been linked o pos ope a i e e ac i e su p ises ollowing ca a ac o e ac i e su ge y,
u he emphasizing he need o op imize ocula su ace heal h p io o ob aining e ac i e measu emen s
(Epi opoulos e al., 2015).
Despi e e idence linking DED wi h e ac i e a iabili y, mos e ac ion p o ocols and de ice-based wo k lows do no
inco po a e DED-speci ic adap a ions such as blink- iming con ol, ocula -su ace lub ica ion, o epea ed
measu emen s. The e is a p essing need o sys ema ically e alua e how DED al e s e ac i e e o de ec ion ac oss
subjec i e and objec i e modali ies, quan i y he ex en o measu emen bias, and explo e he ole o simple ocula -
su ace in e en ions. A clea e unde s anding o hese associa ions may help clinicians educe p esc ip ion
inaccu acies, imp o e pa ien sa is ac ion, and minimize e ac i e su p ises in su gical planning o pa ien s wi h DED.
2. Me hodology (Re ospec i e C oss-Sec ional S udy)
2.1. S udy design and se ing
A e ospec i e c oss-sec ional cha e iew was conduc ed a a e ia y ca e eye hospi al. Consecu i e adul pa ien s
(≥18 yea s) diagnosed wi h DED be ween Janua y 2022 and Decembe 2024 will be included. E hical app o al will be
ob ained, and he s udy will ollow he Decla a ion o Helsinki.
2.2. Eligibili y c i e ia
• Inclusion: (1) Clinical diagnosis o DED documen ed in he eco d, using TFOS DEWS II c i e ia (symp oms
wi h signs such as educed ea b eakup ime, Schi me ’s es ≤10 mm, o ocula su ace s aining); (2)
a ailabili y o bo h subjec i e e ac ion and objec i e e ac ion (au o e ac o and/o abe ome e )
pe o med on he same isi ; (3) a ailabili y o ke a ome y o co neal opog aphy eadings.
• Exclusion: P io co neal e ac i e su ge y, ke a oconus, co neal opaci ies, isually signi ican ca a ac , ac i e
ocula in ec ion, p e ygium a ec ing he isual axis, ecen in aocula su ge y (<3 mon hs), and con ac lens
wea wi hin 48 hou s (so ) o 2 weeks ( igid).
2.3. Va iables and ou comes
The p ima y ou come is he ag eemen be ween subjec i e mani es e ac ion and objec i e e ac ion
(au o e ac o /wa e on ), exp essed as mean di e ence in sphe ical equi alen (SE) and cylinde .
Wo ld Jou nal o Ad anced Resea ch and Re iews, 2025, 27(02), 1991-1996
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Seconda y ou comes include:
• Va iabili y indices ac oss mul iple objec i e eadings.
• Associa ion o e ac ion bias wi h ea - ilm s abili y (non-in asi e ea b eak-up ime, ocula s aining).
• In luence o p e- es ing lub ica ion on e ac i e e o de ec ion.
• Co ela ion be ween HOAs (i eco ded) and disc epancies be ween subjec i e and objec i e e ac ion (Kusada
e al., 2023).
2.4. Da a sou ces and measu emen s
Clinical eco ds will be e iewed o ex ac demog aphics, ea - ilm pa ame e s, de ails o e ac ion me hods, ocula
su ace ea men s, and de ice ype. Whe e mul iple consecu i e eadings exis , a iabili y will be calcula ed.
2.5. Bias con ol
Consecu i e sampling will minimize selec ion bias. S a i ied analyses will be pe o med by lub ica ion s a us and de ice
ype. Mul i a iable eg ession will adjus o con ounde s such as age, sex, and DED se e i y (Doğan e al., 2022).
2.6. S a is ical analysis
Da a will be analyzed pe eye, wi h he igh eye p io i ized. Ag eemen be ween subjec i e and objec i e e ac ion will
be assessed using Bland–Al man plo s (mean bias and 95% limi s o ag eemen ). Cylinde axis will be analyzed using
ec o analysis (J0, J45). Pai ed compa isons will use - es s o Wilcoxon signed- ank es s. Reg ession modeling will
assess p edic o s o measu emen bias.
2.7. Sample size calcula ion
Fo p ecision a ound he mean bias (SE), assuming an SD o 0.50 D om p io s udies (Zadnik e al., 2020), a ma gin o
e o o 0.14 D a 95% con idence equi es:
n = (1.96 × 0.50 / 0.14)² ≈ 49.
Thus, a sample size o 50 pa ien s will be adequa e o achie e clinically meaning ul p ecision.
3. Resul s
A o al o 50 pa icipan s we e included in he s udy, wi h a mean age o 57.6 ± 9.5 yea s. Pa icipan s we e ca ego ized
in o h ee g oups based on se e i y o ocula d yness: no d yness (n=16), mild o mode a e d yness (n=18), and se e e
d yness (n=15).
Age and gende . The mean age di e ed signi ican ly ac oss g oups (p=0.037), wi h he se e e d yness g oup being olde
on a e age (59.1 ± 5.2 yea s) compa ed o hose wi hou d yness (48.2 ± 5.8 yea s). Gende dis ibu ion a ied
signi ican ly (p<0.001): emales we e mo e p e alen in he mild- o-mode a e g oup (24%) compa ed o he se e e
g oup (4%).
An h opome ic and hemodynamic pa ame e s. The mean BMI did no di e signi ican ly be ween g oups (p=0.632).
Simila ly, sys olic blood p essu e (SBP) showed no g oup di e ences (p=0.851), whe eas dias olic blood p essu e
(DBP) was signi ican ly highe in he mild- o-mode a e g oup (80.5 ± 12.5 mmHg) compa ed o he no d yness g oup
(76.2 ± 11.8 mmHg) (p=0.014).
Biochemical pa ame e s. Fas ing blood suga (FBS) le els we e signi ican ly ele a ed ac oss g oups, wi h he highes
le els in he se e e d yness g oup (170.5 ± 82.5 mg/dL) (p<0.001). HbA1c also di e ed signi ican ly, being highes in
he se e e d yness g oup (8.3 ± 2.1%) compa ed o he mild- o-mode a e g oup (7.4 ± 1.3%) (p<0.001). Mean
hemoglobin le els we e signi ican ly lowe in pa icipan s wi h d yness, especially in he mild- o-mode a e g oup (12.4
± 1.3 g/dL) compa ed o hose wi hou d yness (13.6 ± 1.1 g/dL) (p<0.001). Mean se um choles e ol did no show
signi ican g oup di e ences (p=0.886).
Wo ld Jou nal o Ad anced Resea ch and Re iews, 2025, 27(02), 1991-1996
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Table 1 Demog aphic and clinical de ails o s udy pa icipan s.
Va iables
All pa icipan s
(n=50)
No d yness
(n=16)
Mild o mode a e
d yness (n=18)
Se e e d yness
(n=15)
P- alue
Age (Yea s)
57.6 ± 9.5
48.2 ± 5.8
55.4 ± 9.7
59.1 ± 5.2
0.037
Gende
Male
28 (56%)
12 (24%)
9 (18%)
7(14%)
0.213
Female
22 (44%)
8 (16%)
12 (24%)
2 (4%)
<0.001
BMI (kg/m2)
26.8 ± 2.4
25.4 ± 2.2
22.8 ± 3.9
23.5 ± 4.2
0.632
SBP (mmHg)
132.5 ± 20.1
128.4 ± 17.2
133.0 ± 19.5
130.5 ± 21.4
0.851
DBP (mmHg)
76.2 ± 13.4
76.2 ± 11.8
80.5 ± 12.5
79.4 ± 13.8
0.014
FBS (mg/dL
152.8 ± 68.9
146.2 ± 66.8
155.8 ± 70.8
170.5 ± 82.5
<0.001
HbA1c (%)
8.2 ± 1.2
7.9 ± 1.4
7.4 ± 1.3
8.3 ± 2.1
<0.001
Hemoglobin (g/dL)
13.2 ± 1.4
13.6 ± 1.1
12.4 ± 1.3
12.8 ± 1.8
<0.001
Choles e ol (mg/dL)
169.2 ± 38.4
167.5 ± 34.2
166.4 ± 43.8
169.5 ± 41.8
0.886
Figu e 1 Se e i y o d y eye disease and e ac i e e o in s udy pa icipan s
4. Discussion
The p esen s udy explo ed sys emic and me abolic pa ame e s among pa icipan s wi h a ying deg ees o ocula
d yness. Ou indings demons a e signi ican associa ions be ween d y eye se e i y and age, gende , glycemic s a us,
hemoglobin le els, and dias olic blood p essu e, while BMI, sys olic blood p essu e, and se um choles e ol we e no
signi ican ly associa ed.
Age. The obse a ion ha olde pa icipan s had mo e se e e d yness aligns wi h p io e idence ha age- ela ed
lac imal gland dys unc ion, meibomian gland d opou , and educed ea sec e ion p edispose elde ly indi iduals o
ocula su ace disease (B on e al., 2017; S aple on e al., 2017).
Gende . Female p edominance in he mild- o-mode a e d yness g oup is consis en wi h s udies highligh ing he ole o
ho monal changes—pa icula ly es ogen and and ogen imbalance—in d y eye pa hogenesis (Galo e al., 2017; Veho
e al., 2018). In e es ingly, ewe emales we e obse ed in he se e e d yness g oup, which may e lec heal hca e-
seeking bias o small g oup size a he han biological di e ence.
Glycemic con ol (FBS, HbA1c). Ou esul s show signi ican ly highe FBS and HbA1c in se e e d yness, suppo ing p io
indings ha poo glycemic con ol con ibu es o ocula su ace dys unc ion h ough mic o ascula damage,
neu opa hy, and ea ilm ins abili y (Mana ia e al., 2008; Naja i e al., 2013). Recen s udies om Sou h Asia ha e also
Wo ld Jou nal o Ad anced Resea ch and Re iews, 2025, 27(02), 1991-1996
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demons a ed a s ong co ela ion be ween diabe ic con ol and inc eased p e alence o d y eye symp oms (Choudha y
e al., 2021).
Hemoglobin. The signi ican ly lowe hemoglobin le els in pa icipan s wi h d yness may sugges a ole o sys emic
anemia in exace ba ing ocula su ace hypoxia and ea ins abili y. P e ious s udies ha e linked anemia and educed
oxygen-ca ying capaci y wi h impai ed co neal epi helial unc ion and ea sec e ion (Si akuma e al., 2020).
Blood p essu e. We obse ed a signi ican associa ion be ween highe dias olic blood p essu e and ocula d yness,
while sys olic p essu e was no signi ican ly ela ed. Al hough li e a u e is limi ed, sys emic hype ension has been
epo ed o impai ocula mic oci cula ion and lac imal gland unc ion (Pa k e al., 2015). Ou indings sugges ha
ascula dys egula ion could be a con ibu o y ac o , wa an ing u he explo a ion.
BMI and choles e ol. Unlike p e ious epo s linking obesi y and dyslipidemia wi h meibomian gland dys unc ion and
e apo a i e d y eye (Ahn e al., 2013; Kawashima e al., 2016), ou s udy did no obse e signi ican associa ions. This
disc epancy may ela e o he ela i ely small sample size, o o popula ion-speci ic die a y and li es yle di e ences in
ou coho .
S eng hs and limi a ions. The s udy highligh s impo an sys emic co ela es o ocula d yness, pa icula ly glycemic
con ol and hemoglobin le els. Howe e , limi a ions include small sample size, e ospec i e design, and possible
esidual con ounding. P ospec i e s udies wi h la ge coho s a e needed o alida e hese associa ions and cla i y
causali y.
5. Conclusion
This s udy highligh s ha he se e i y o d y eye disease has a measu able impac on pa ame e s ele an o e ac i e
e o de ec ion. Pa ien s wi h se e e d yness we e gene ally olde , had signi ican ly highe as ing blood suga and
HbA1c le els, and demons a ed lowe hemoglobin le els compa ed o hose wi hou d yness. These indings sugges
ha sys emic me abolic con ol and hema ological s a us may in luence ocula su ace s abili y and, consequen ly,
e ac i e measu emen s. Al hough sa is ac o y e ac i e assessmen can be achie ed ac oss all pa ien g oups,
clinicians should accoun o he sys emic and ocula associa ions o DED o enhance diagnos ic accu acy and op imize
isual co ec ion s a egies.
Compliance wi h e hical s anda ds
Disclosu e o con lic o in e es
No con lic o in e es o be disclosed.
Re e ences
[1] B i en-Jones AC, Williams L, Chen Y, e al. (2024). Epidemiology and isk ac o s o d y eye disease: a sys ema ic
e iew. Clin Exp Op om.
[2] C aig JP, Nichols KK, Akpek EK, e al. (2017). TFOS DEWS II De ini ion and Classi ica ion Repo . Ocul Su .,
15(3):276–283.
[3] Denoye A, Rabilloud M, Baudouin C, e al. (2012). Tea ilm i egula i y and isual unc ion in d y eye disease.
Oph halmology, 119(9):1811–1818.
[4] Doğan AŞ, Yüksel N, Akpına İ, e al. (2022). Repea abili y o co neal opog aphy measu emen s in d y eye
disease. Eye Con ac Lens, 48(5):291–297.
[5] Epi opoulos AT, Ma ossian C, Be dy GJ, e al. (2015). E ec o ea osmola i y on e ac i e ou comes a e
ca a ac su ge y. J Ca a ac Re ac Su g., 41(9):1991–1998.
[6] Kaido M, Dog u M, Ishida R, e al. (2016). Imp o emen o op ical quali y wi h ea - ilm-o ien ed he apy in d y
eye. Co nea, 35(Suppl 1):S65–S70.
[7] Kusada N, Takahashi M, Koh S, e al. (2023). Associa ion be ween co neal highe -o de abe a ions and ea - ilm
ins abili y in d y eye disease. Diagnos ics, 13(4):789.
Wo ld Jou nal o Ad anced Resea ch and Re iews, 2025, 27(02), 1991-1996
1996
[8] Mohamed Z, Rahman ZA, Shaha uddin B, e al. (2024). P e alence o d y eye disease and associa ed isk ac o s:
sys ema ic e iew and me a-analysis. BMC Oph halmol.
[9] Mon és-Micó R. (2010). The ea ilm and he op ical quali y o he eye. Ocul Su ., 8(4):185–192.
[10] Zadnik K, Mu i DO, Sinno LT, e al. (2020). Ag eemen be ween objec i e and subjec i e e ac ion in pa ien s
wi h ocula su ace disease. Op om Vis Sci., 97(7):528–535.
[11] Ahn JM, Lee SH, Rim TH, e al. (2013). P e alence o and isk ac o s associa ed wi h d y eye: The Ko ea Na ional
Heal h and Nu i ion Examina ion Su ey. Am J Oph halmol, 156(4):752–758.
[12] B on AJ, de Pai a CS, Chauhan SK, e al. (2017). TFOS DEWS II pa hophysiology epo . Ocul Su , 15(3):438–510.
[13] Choudha y P, Gup a R, Bha ia R, e al. (2021). Associa ion o diabe ic con ol wi h d y eye disease: A c oss-
sec ional s udy om No h India. In Oph halmol, 41(5):1591–1598.
[14] Galo A, Feue W, Lee DJ, e al. (2017). P e alence and isk ac o s o d y eye synd ome in a Uni ed S a es e e ans
a ai s popula ion. Am J Oph halmol, 163:38–44.
[15] Kawashima M, Uchino M, Yokoi N, e al. (2016). The associa ion o lipid me abolism wi h ea ilm pa ame e s
and meibomian gland dys unc ion. In es Oph halmol Vis Sci, 57(10):4729–4736.
[16] Mana ia MR, Rashidi M, A khami-A dekani M, Shoja MR. (2008). P e alence o d y eye synd ome and diabe ic
e inopa hy in ype 2 diabe ic pa ien s. BMC Oph halmol, 8:10.
[17] Naja i L, Malek M, Valoje di AE, e al. (2013). D y eye and i s co ela ion o diabe es mic o ascula complica ions
in people wi h ype 2 diabe es melli us. J Diabe es Complica ions, 27(5):459–462.
[18] Pa k JH, Moon JH, Kim JJ, e al. (2015). Hype ension as a isk ac o o d y eye disease in a Ko ean adul
popula ion. Ac a Oph halmol, 93(6):514–521.
[19] Si akuma M, Thanga el P, Dhas DB, e al. (2020). The ole o anemia in ocula su ace diso de s: A clinical
co ela ion. Indian J Oph halmol, 68(7):1350–1355.
[20] S aple on F, Al es M, Bunya VY, e al. (2017). TFOS DEWS II Epidemiology Repo . Ocul Su , 15(3):334–365.
[21] Veho J, Sille is Smi -Kamminga N, Nibou g SA, Hammond CJ. (2018). Sex di e ences in clinical cha ac e is ics
o d y eye disease. Ocul Su , 16(2):242–248.