INFLUENCE OF CENTRAL CORNEAL THICKNESS ( CCT ) ON THE INTRAOCULAR PRESSURE ( IOP ) MEASUREMENTS TAKEN FROM GOLDMANN APPLANATION TONOMETER , TONOPEN , AND AIRPUFF TONOMETER

Affiliation 1. Fellow of Vitreo-Retinal Surgery, Lumbini Eye Institute, Lumbini, Nepal 2. Lecturer, B.P.Koirala Lions Centre for Ophthalmic Studies, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal 3. Resident, Department of Ophthalmology, Nepalese Army Institute of Health Sciences, Kathmandu, Nepal 4. M.D Ophthalmologist, B.P.Koirala Lions Centre for Ophthalmic Studies, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal 5. Resident, B.P.Koirala Lions Centre for Ophthalmic Studies, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal 6. Resident, Lumbini Eye Institute, Lumbini, Nepal


Objec ve
In this study, we a empt to determine the agreement and influence of the central corneal thickness in the measurement of IOP obtained by Goldman applana on tonometer, Airpuff tonometer and tonopen.

Methodology
A cross-sec onal analy cal study of Central corneal thickness (CCT) was done using Ultrasonic pachymetry.IOP was adjusted using Ehler's formula.Mean and the standard devia on was measured using the observed and predicted values for each instrument for its accuracy irrespec ve of the CCT.

Results
200 eyes of 100 pa ents were included in the study.Mean IOP measured was 16mmHg (SD 4).Tonopen was found to have closer observed values when compared with the predicted values to IOP obtained by Goldmann's applana on tonometer a er CCT adjustments with Mean difference of 0.0134mmHg with SD of 0.814.Air Puff tonometer was found to be the least accurate with Mean difference -2.08mmHg and SD of 4.704.Linear regression analysis also predicted that while the tonopen tend to underes mate the IOP levels by 5 %, Airpuff tonometer had a tendency to overes mate the IOP by 13%.(p<0.05)

Conclusion
Tonopen had the greatest agreement and significant correla on with the GAT over a range of IOP and CCT and replicate measurements that are closest to the values obtained by using GAT a er CCT adjustments.CCT adjustments may not even be required or has very li le influence on IOP when using Tonopen.

INTRODUCTION
Glaucoma is a chronic and o en progressive op c neuropathy with typical structural and func onal changes in the op c nerve head.Intraocular pressure (IOP) remains 1-3 the one and an only adjustable risk factor for glaucoma .A normal IOP is necessary to maintain the integrity of the eye and its visual func on.A prolonged eleva on in IOP o en results in irreversible damage to the re nal ganglion cells 4,5 and postganglionic nerve fibers.Elevated IOP is not the 6-8 cause of all damage in POAG-but a major risk factor.The issue of IOP, however, has been made controversial by corneal thickness-which is both a parameter that may cause inaccurate readings with applana on tonometry and an independent factor that may be predic ve of the risk of 9 developing open-angle glaucoma.The mechanism by which elevated IOP damages the op c nerve is not clear, but ischemia of the op c disc or nerve fiber layer, direct mechanical compression of axons, local toxicity, or some combina on of these has been implicated.
One of its variant and the most common form-Primary open-angle glaucoma (POAG) is a chronic, progressive, anterior op c neuropathy that is associated with characteris c cupping and atrophy of the op c disc, visual field loss, open 10 angles, and no obvious causa ve ocular or systemic condi ons.POAG accounts for nearly three-quarters (74%) of all 11,12 glaucoma cases.In most cases, es mates, and Metaanalysis data show that es mated there could be 60.5 million people with Open Angle Glaucoma (OAG) and Angle 11,13 Closure Glaucoma (ACG) in 2010.
The 1981 Nepal Blindness Survey es mated that there were 117,623 blind people in Nepal.Glaucoma was found to be an important cause accoun ng for 3.2% a er cataract (66.8%) and re nal diseases (3.3%).Recent data collected at regional or district levels have shown that even if one is considering the lowest POAG prevalence to make a na onwide es mate, such as 3.25% for the Tharu ethnic group in our study, this would tenta vely suggest 645,585 people with POAG in Nepal.It can be addi onally es mated 14 that 30,342 people could be blind in Nepal due to POAG.
There has been a rapid development of tonometry instruments in recent years to ensure a more accurate  Goldmann and Schmidt hypothesized that surface tension and corneal rigidity would nullify one another and would not influence the IOP measurements if the contact that the tonometer would make to the cornea is 3.06 mm in diameter.
The concept of Applana on tonometry is derived from the Imbert-Fick law, It works on the principle that the force required to fla en a sphere is equal to the product of the pressure at which the sphere is inflated and the area applanated.The criteria that must be met for the above law to be applicable are-the surface is dry, flexible, thin and spherical as possible.
When we are measuring the IOP of an eye using applana on, we must keep in mind the two major forces that will influence the measurements.The surface tension of the tear film-although in microlevels -it tends to pull the tonometer head toward the cornea and increase applana on.The corneal rigidity then starts its part.It is o en considered at the force required to bend the cornea-which also resists 23 applana on.
The calcula ons were based on assump ons that the pressure required to fla en the cornea would be the same for all corneas.However, if a cornea is thicker than the average, it seems sensible to have to be applanted by a greater force.
GAT measurement was found to be influenced by the individual's central corneal thickness.If changes in the central corneal thickness are not considered, GAT assumes a 23 standard of 520 μm for all corneas.In most studies, the 24 normal range was from 427 to 620 μm. 25 Intraocular pressure (IOP) is one of the basic inves ga ons.It is the only modifiable risk factor for the development and and its adjacent ssues Furthermore, IOP-inflicted impact can also compress lamina cribrosa and interfere with the axonal transport of trophic factors indispensable for the 28 auto-regula on, and survival of re nal ganglion cells.Since lamina cribrosa is the loca on where re nal ganglion cell axons cluster before they pass through the brain, unwarranted mechanical strain can cause glaucoma damage to this 27 structure.
In the 1970s, Ehlers et al carried out a number of studies to [29][30][31] evaluate the impact of CCT on IOP.From their manometric report, it was shown that the average tonometry error was 0.71 mmHg for a 10 μm CCT devia on of 520 μm.Johnson et al reported a 900 μm CCT pa ent with 11 mmHg 32 33 manometric IOP.Whitacre illustrated an overstatement of IOP of as much as 4.9 mmHg in thin corneas in a manometric study with the Perkins tonometer, with thick corneas producing an overes ma on of as much as 6.8 mmHg.This conversed to a calculated range of 0.18 to 0.49 mmHg IOP change for a 10-μm CCT change from the mean CCT.This showed that the rela onship of CCT on IOP was not linear and IOP had to be corrected for over or underes ma on using the CCT values.
Most cases of POAG are discovered through screening  Intraocular pressure was taken with the help of Goldmann applana on tonometer.Proparacaine hydrochloride ophthalmic solu on USP, 0.5% was ins lled in both eyes and a er 30 seconds, gonioscopy was performed using indent able Volk 6 mirror gonioscopy.(Volk G-6 Six-Mirror Glass ).Spaeth's gonioscopic grading done.IOP was then measured using GAT, air puff tonometer, and tonopen.
Central corneal thickness (CCT) was measured using Ultrasonic pachymetry.IOP measured using GAT was considered as gold standard.Ehlers formula (over or underes ma on of IOP by 0.5mmHg for every 10-micrometer change in central corneal thickness taking 520 micrometers as standard where no adjustments are to be made) was used to adjust the observed IOP by various instruments.Mean and the standard devia on was measured using the observed and predicted values for each instrument.
Preformed proforma designed for this study was used to record the relevant history and clinical findings.

RESULTS
Tonopen was found to have closer observed values when compared with the predicted values to IOP obtained by Goldmann's applana on tonometer a er CCT adjustments with Mean difference of 0.0134 with SD of 0.814 (p=0.036).
(Figure 1 and Figure 2) .Air Puff tonometer was found to be the least accurate with Mean difference -2.08 and SD of 4.704.Linear regression analysis also showed that while the tonopen tend to underes mate the IOP levels by 5 %, Airpuff tonometer had a tendency to overes mate the IOP by 13% and error in measurements were significant to cause devia on from actual readings and was found to be less reliable (p=0.159)(Figure 3 and Figure 4)

DISCUSSION
Our study was done to report the agreement of the IOP measurements obtained using different devices by comparing it with the IOP measured using GAT -which were adjusted for CCT.
The dual advantages of being portable and availability may make the tonopen tonometer a popular choice among ophthalmology trainees and optometrists in a developing country like Nepal.A good documenta on of the previous IOP along with the equipment used is a must to analyze the effec veness of treatment if the pa ent is receiving any for their condi ons.Tonopen had the greatest agreement and significant correla on with the GAT over a range of IOP and CCT.A study done by A Bhan et al, have also reported similar finding in their study where they have concluded that the Tono-Pen was the least influenced and minimally affected by CCT 39 when used to measure IOP in eyes with normal corneas.They have also reported that the pneumotonometer appears to be more affected by varia on in CCT than the Goldmann tonometer.This study also shows that tonopen can be recommended and used and its measurements are closest to the values obtained by using GAT a er CCT adjustments.40 Shields also concluded from his paper that NCT was less reliable in pa ents with elevated IOP and had a poorer correla on with GAT at higher ranges.
In another similar study done in the region by Nagarajan et al, they have also concluded from their study that the tonopens were least affected by CCT and showed accurate readings correla ng with GAT readings that were adjusted 41 19 with CCT.Tonnu el al also had compared contact and noncontact tonometer in their study for its precision and accuracy.They also concluded that there was an appreciable inter-observer agreement with the GAT while NCT were found to be less accurate.
Tonopen is an accurate and reliable screening tool in community outreach ophthalmology services or even in ter ary eye care setup.It doesn't require any special stain and is not dependant upon the observer to match the mires for measuring the IOP.

CONCLUSION
Goldmann Tonometer remains the gold standard and the most accurate IOP measuring devices for a wide range of CCT.Airpuff although quick, is bulky equipment and its reading seems to deviate with extremes of IOP and tends to have the least accuracy among the three equipments.

RECOMMENDATIONS
Modern inves ga ve tools like Tonopen can be recommended as a reliable diagnos c tool for glaucoma/glaucoma suspects.It can aid in keeping a track of intraocular pressure accurately.

LIMITATION OF THE STUDY
Our knowledge base is built on uncovering each piece of the puzzle, one at a me, and limita ons show us where new efforts need to be made.In the end, we hope our limita on may be someone else's inspira on.A larger popula on group and an anterior segment Op cal Coherence Tomography (OCT) or Wavefront analyzer for evalua on of the CCT would have made the findings more accurate.Since our study was performed at a ter ary center in the eastern region of Nepal, factors such as a strong regional focus, being too popula on-specific, or the field being only conducive to incremental findings could be an impact-limi ng factor.Due to the me restric on and study being conducted in a single center, perhaps enrollment was more difficult than expected, under powering our results.

15 - 17 measurement
of IOP.However, confounding forces such as Central corneal thickness (CCT) cause inaccuracy in its 18-20 measurement.CCT is an established independent predictor for the development of primary open-angle glaucoma (POAG) as per the Ocular Hypertension 7 Treatment Study (OHTS) and the European Glaucoma 21 Preven on Study (EGPS).It has been postulated that the risk of POAG doubled for every 40 μm decrease in CCT from the overall mean of 573.3μm from the OHTS and EGPS 22 pooled sample.

23
of POAG It has been assumed that increased IOP stresses the op c nerve head ( ONH) and lamina cribrosa7,26,27

METHODOLOGYA
cross-sec onal analy cal study in which IOP was measured in 200 eyes of 100 pa ents using the three tonometers.Over a 2 month, pa ents of both sexes between the ages of 16-80 years a ending the outpa ent services were randomly screened and included in this study.This study was conducted at ter ary eye care center -Birat eye st Hospital in Nepal and the repor ng period was from 1 May st 2018 to 1 July 2018.The protocol was reviewed and approved by the ethics commi ee and adheres with the tenets of the Declara on of Helsinki.Diagnosed cases of POAG regardless of gender along with the stage fulfilling the diagnos c criteria a ending OPD were included in the study.Pa ents having narrow-angle in either eye or with PACG or any history of intraocular surgery (E.g.: Vitreo-re nal Procedures, Glaucoma Filtra on surgeries), secondary open angle-closure glaucoma, inflammatory glaucoma, acute conges ve glaucoma, corneal anomaly, scarring or abnormali es that may cause irregular surface or thickness and op c disc anomalies were excluded.Visual Acuity was taken using standard Snellen's chart and tumbling E chart, Conjunc va, episclera, and sclera were examined using Haag Streit 900 slit lamp to see any secondary causes/ post-trabeculectomy and other surgical scars.)Detailed fundus examina on under mydriasis using eye drop Tropicamide 1% was performed with Heine Beta 200 direct ophthalmoscope, binocular indirect ophthalmoscopy with +20D lens and Haag Streit 900 slit lamp with +90D lens whenever indicated and feasible.
200 eyes of 100 pa ents were included in the study.The study popula on comprised of 47 percent males with mean age of 51 years (95% CI 51.8-57.5, range 26-78 years) and 53 percent females with mean age of 53.6 years (95% CI 49.2-55.7,range 20-80 years).The mean age of all pa ents in this study was 55.2 years (95% CI 54.3-55.9years).The youngest pa ent enrolled was of 32 years and the oldest being 85 years.The mean CCT was 532.7 microns (μm) (95% CI 521.6-538.5)ranging between 469 μm and 576 μm.

Figure 1 :Figure 2 :
Figure 1: to maintain good visual func on for the life of the pa ent and to prevent interference with the quality of 36,37programs or on rou ne ocular examina ons Measurement and recording of IOP are required not only in ini a ng treatment but also in monitoring the response to treatment36,37and progression of the disease.The main objec ve of treatment is