1 Surowe wyniki pomiarów ciśnienia śródgałkowego (IOP) w oku prawym (OD) i lewym (OS) w ostatnich kilku dobach

Raw IOP measurements in the right (OD) and left (OS) eye over the last few days

2 Ciśnienie w oku prawym i lewym z wygładzonym wahaniem dobowym

Smoothed IOP curves for both eyes

3 Różnica ciśnienia między prawym a lewym okiem

Right minus left eye IOP difference
19.11 zamieniono oczami (1) NodoFreeCombi i (2) TimoComod + Azopt
2.12 OS bez zmian NodoFree Combi, w OD zmiana na Vizitrav + NodoFree Combi
9.12 OD bez zmian, w OS włączono Vizitrav

Treatment crossed over between eyes on Nov. 19
Dec 2nd OD stays on NodoFree Combi, OS switched to Vizitrav + NodoFree Combi
Dec 9th Vizitrav added in OS

4 Model z uwzględnieniem pory dnia, schematu leczniczego i oka

Polynomial model with hour of the day, treatment and eye as predictors

4.1 Parametry modelu

Poziom odniesienia to oko prawe (OD), NodoFree Combi. Krople działają multiplikatywnie raczej niż addytywnie, stąd log(IOP) jako zmienna objaśniana.

Model parameters with right eye and NodoFree Combi as reference levels. IOP-lowering drops work in a multiplicative rather than additive fashion, thus we predict log(IOP).

## 
## Call:
## lm(formula = log(IOP) ~ Eye + Treatment + poly(Hour, 5), data = IOP[IOP$Date > 
##     from, ])
## 
## Residuals:
##      Min       1Q   Median       3Q      Max 
## -0.56109 -0.14674  0.00623  0.14845  0.47530 
## 
## Coefficients:
##                          Estimate Std. Error t value Pr(>|t|)    
## (Intercept)               2.82220    0.02018 139.865  < 2e-16 ***
## EyeOS                    -0.11618    0.01813  -6.408 2.77e-10 ***
## TreatmentTimo+Azopt       0.03654    0.02364   1.546   0.1227    
## TreatmentTravo+NodoCombi -0.27120    0.02014 -13.466  < 2e-16 ***
## poly(Hour, 5)1           -1.19215    0.20904  -5.703 1.76e-08 ***
## poly(Hour, 5)2            0.17975    0.20873   0.861   0.3895    
## poly(Hour, 5)3           -0.49078    0.20908  -2.347   0.0192 *  
## poly(Hour, 5)4           -2.60410    0.20901 -12.459  < 2e-16 ***
## poly(Hour, 5)5            0.94617    0.20876   4.532 6.90e-06 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Residual standard error: 0.2087 on 677 degrees of freedom
## Multiple R-squared:  0.4551, Adjusted R-squared:  0.4487 
## F-statistic: 70.68 on 8 and 677 DF,  p-value: < 2.2e-16

Współczynniki powyższe są wykładnikami logarytmu naturalnego: Po ich “odlogarytmowaniu” dostajemy poniższe współczynniki. Mówią one, że ciśnienie śródgałkowe dla wartości odniesienia (= oko prawe, NodoFree Combi) wynosi 16.8 mm Hg, w oku lewym ciśnienie jest niższe o -11%, natomiast dodanie travoprostu (Vizitrav) do NodoFree Combi daje dodatkową redukcję IOP o -24%. Wpływ pory doby zilustrowano na wykresie efektu godziny poniżej.

Estimates are natural logs, after exponentiating we obtain coefficients as below. The model thus predicts an IOP of 16.8 mm Hg in the right eye using NodoFree Combi, left eye pressure being lower by -11%, whereas adding travoprost drops (Vizitrav) to NodoFree Combi results in an additional IOP reduction of -24%. For hour-of-the-day effect, see the plot below.

##                           IOP
## (Intercept)              16.8
## EyeOS                    -11%
## TreatmentTimo+Azopt        4%
## TreatmentTravo+NodoCombi -24%

4.2 Wykresy efektów oka i schematu leczniczego

Effect plots

4.3 Wykres efektu pory dnia

5 Dobowe maksima, minima i wartości środkowe

Daily maximum, minimum, and mid-range

6 Modele dla wartości dobowych

Models for daily values
Poziom odniesienia to oko prawe (OD), NodoFree Combi.

Reference levels are for right eye and NodoFree Combi.

6.1 Dobowe wartości środkowe (między maksimum i minimum)

Daily mid-range values (between max and min)

## 
## Call:
## lm(formula = log(IOP.day.mid) ~ Eye + Treatment, data = daily.s)
## 
## Residuals:
##      Min       1Q   Median       3Q      Max 
## -0.33599 -0.05368  0.01954  0.05552  0.18653 
## 
## Coefficients:
##                          Estimate Std. Error t value Pr(>|t|)    
## (Intercept)               2.85799    0.02269 125.945  < 2e-16 ***
## EyeOS                    -0.07965    0.02130  -3.740  0.00035 ***
## TreatmentTimo+Azopt       0.01285    0.02651   0.485  0.62928    
## TreatmentTravo+NodoCombi -0.23936    0.02456  -9.747 3.87e-15 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Residual standard error: 0.09017 on 78 degrees of freedom
## Multiple R-squared:  0.6397, Adjusted R-squared:  0.6258 
## F-statistic: 46.15 on 3 and 78 DF,  p-value: < 2.2e-16
##                           IOP
## (Intercept)              17.4
## EyeOS                     -8%
## TreatmentTimo+Azopt        1%
## TreatmentTravo+NodoCombi -21%

6.2 Dobowe wartości minimalne

Daily minimum

## 
## Call:
## lm(formula = log(IOP.day.min) ~ Eye + Treatment, data = daily.s)
## 
## Residuals:
##       Min        1Q    Median        3Q       Max 
## -0.273517 -0.102376 -0.008518  0.096842  0.309184 
## 
## Coefficients:
##                          Estimate Std. Error t value Pr(>|t|)    
## (Intercept)               2.46999    0.03216  76.798  < 2e-16 ***
## EyeOS                    -0.11703    0.03019  -3.877 0.000219 ***
## TreatmentTimo+Azopt       0.05200    0.03757   1.384 0.170229    
## TreatmentTravo+NodoCombi -0.26425    0.03480  -7.593 5.77e-11 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Residual standard error: 0.1278 on 78 degrees of freedom
## Multiple R-squared:  0.5663, Adjusted R-squared:  0.5496 
## F-statistic: 33.94 on 3 and 78 DF,  p-value: 3.846e-14
##                           IOP
## (Intercept)              11.8
## EyeOS                    -11%
## TreatmentTimo+Azopt        5%
## TreatmentTravo+NodoCombi -23%

6.3 Dobowe wartości maksymalne

Daily maximum

## 
## Call:
## lm(formula = log(IOP.day.max) ~ Eye + Treatment, data = daily.s)
## 
## Residuals:
##      Min       1Q   Median       3Q      Max 
## -0.43309 -0.07145  0.01890  0.06335  0.19859 
## 
## Coefficients:
##                           Estimate Std. Error t value Pr(>|t|)    
## (Intercept)               3.133618   0.027573 113.650  < 2e-16 ***
## EyeOS                    -0.061472   0.025878  -2.375    0.020 *  
## TreatmentTimo+Azopt      -0.007034   0.032206  -0.218    0.828    
## TreatmentTravo+NodoCombi -0.228111   0.029837  -7.645 4.57e-11 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Residual standard error: 0.1096 on 78 degrees of freedom
## Multiple R-squared:  0.4977, Adjusted R-squared:  0.4784 
## F-statistic: 25.76 on 3 and 78 DF,  p-value: 1.108e-11
##                           IOP
## (Intercept)                23
## EyeOS                     -6%
## TreatmentTimo+Azopt       -1%
## TreatmentTravo+NodoCombi -20%

7 Efekt obniżenia ciśnienia śródgałkowego po ćwiczeniu: bezpośrednio po 10-minutowej jeździe rowerem, umiarkowany wysiłek

IOP drop and return to baseline following 10-minute moderate cycling