Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 29  |  Issue : 2  |  Page : 80-88

Predictors of Clinical Outcome of Ulcerative Keratitis in a Tertiary Hospital


1 Department of Ophthalmology, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu; Department of Ophthalmology, Alex Ekwueme Federal University Teaching Hospital Abakaliki, Ebonyi, Nigeria
2 Department of Ophthalmology, University Nigeria of Teaching Hospital, Ituku-Ozalla, Enugu; Department of Ophthalmology, Alex Ekwueme Federal University Teaching Hospital Abakaliki, Ebonyi, Nigeria
3 Department of Ophthalmology, Alex Ekwueme Federal University Teaching Hospital Abakaliki, Ebonyi, Nigeria
4 Department of Ophthalmology, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu; Department of Ophthalmology, Enugu State University Teaching Hospital Parklane, Enugu, Nigeria

Date of Submission19-Mar-2020
Date of Decision03-Oct-2020
Date of Acceptance27-Jul-2021
Date of Web Publication18-Jan-2022

Correspondence Address:
O. C. Arinze
Department of Ophthalmology, Alex Ekwueme Federal University, Abakaliki Ebonyi
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njo.njo_11_20

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  Abstract 


Aims and objectives: To determine the predictors of clinical outcome of ulcerative keratitis at the University of Nigeria Teaching Hospital, Enugu, Nigeria. Methods: This was a hospital-based study of 61 patients with ulcerative keratitis. Participants’ sociodemographics and clinical information were obtained. Outcome measures included treatment outcome (categorized into good treatment outcome and poor treatment outcome) and posttreatment visual outcome (categorized into visual acuity 6/60 or better and visual acuity worse than 6/60). Results: A total of 61 patients were recruited for the study. Of these, 44 (72.1%) were males and 17 (27.9%) were females. Although majority 55 (90.1%) of the ulcers healed, many developed complications such as perforation with evisceration − 3 (11.5%), panopthalmitis with evisceration − 3 (11.5%), healed perforated ulcers with visually significant adherent leukoma − 5 (19.2%), visually significant corneal opacities from ulcers that healed without perforation − 6 (23.1%), corneal vascularizattion − 7 (26.9%), and anterior staphloma − 2 (7.7%). Predictors of poor treatment outcome included duration of symptoms of more than 1 week, use of harmful traditional eye medictions (TEMs), size of ulcer ≥4mm, and presence of hypopyon. Significant predictors of poor posttreatment visual outcome included age 40 years and above, size of ulcer ≥4 mm, and duration of symptoms ≥1 week. Conclusions: Majority of the corneal ulcers healed. However, many also had complications that led to significant visual impairment and ocular morbidity. These are largely due to late presentation and indiscriminate use of TEMs. Effective eye health education and promotion are recommended to encourage early presentation, prevention, and reduction of visual and ocular morbidity from ulcerative keratitis.

Keywords: Outcome, predictors, ulcerative keratitis


How to cite this article:
Arinze OC, Ezisi CN, Ogbonnaya CE, Okoloagu NM. Predictors of Clinical Outcome of Ulcerative Keratitis in a Tertiary Hospital. Niger J Ophthalmol 2021;29:80-8

How to cite this URL:
Arinze OC, Ezisi CN, Ogbonnaya CE, Okoloagu NM. Predictors of Clinical Outcome of Ulcerative Keratitis in a Tertiary Hospital. Niger J Ophthalmol [serial online] 2021 [cited 2022 May 22];29:80-8. Available from: http://www.nigerianjournalofophthalmology.com/text.asp?2021/29/2/80/335910




  Introduction Top


In most developing countries, ulcerative keratitis and subsequent corneal scarring is considered one of the leading causes of monocular blindness and ocular morbidity.[1],[2],[3] It has been demonstrated to be responsible for about for 1.5 to 2.0 million new cases of monocular blindness yearly.[4] About 90% of these have been reported to occur in developing countries.[5] Indeed, the World Health Organization global data on the causes of blindness reports corneal opacities as being responsible for about 5.1% of the total number of blind people.[6] The 2005–2007 Nigeria National Blindness and Visual Impairment Survey reported that the prevalence of blindness due to corneal scarring from all causes was 7.9%.[7]

Ulcerative keratitis is considered an ophthalmic emergency because of its potential to permanently impair vision or perforate the eye.[6] The presentation is often acute, with patients often in significant pain and distress.[8] Rapid initiation of aggressive treatment is therefore needed to halt the disease process and limit the extent of corneal scarring and loss of vision.[9]

Since the discovery of antibiotics and the advancement of medical technology, the incidence of microbial keratitis has been drastically reduced in developed countries.[10] However, the incidence of microbial keratitis is still quite high in developing countries, mainly due to lack of medical awareness, or in certain parts, due to inaccessibility to medical treatment.[10] Indeed, treatment of corneal disease in some African communities is often delayed for weeks and patients frequently present to medical facilities with advanced disease including perforated ulcers and completely melted corneas.[11] This has adverse prognostic implications as regards posttreatment clinical outcome .

A better understanding of factors that could predict or prognosticate clinical outcome in ulcerative keratitis therefore becomes imperative as it could potentially be used to improve quality of treatment and subsequently reduce ocular morbidity and visual loss associated with ulcerative keratitis.

The relationship between potential prognostic factors (measurable at the time of diagnosis) and posttreatment clinical outcome, if well characterized and documented could help in planning preventive and treatment programs for ulcerative keratitis. This survey is therefore a response to the need to generate accurate and reliable data on predictors of clinical outcome in patients with ulcerative keratitis.

It is hoped that findings from this study will provide an accurate evidence-based data which will contribute to informed advocacy for policy development, preventive, and interventional program formulation to plug the gap in effective management of ulcerative keratitis.


  Materials and Methods Top


A total of 68 potential incident cases of patients with corneal ulcers were recruited for the study. A total of 61 participants were selected after signing the informed consent form. Seven patients declined participation. All patients were followed up for a minimum of 4 weeks, whereas 57 participants were followed up for a maximum of 12 weeks [Figure 1].
Figure 1 A flow chart representation of the study

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Study design

This was a 1-year hospital-based prospective, descriptive, cross-sectional study of patients with ulcerative keratitis who presented to the Ophthalmic Out-patient Clinic of the University of Nigeria Teaching Hospital (UNTH) Ituku-Ozalla, Enugu State from October 2011 to September 2012.

Ethical clearance

Ethical approval for the study was obtained from the Health Research Ethics Committee of the University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, prior to its commencement.

Informed consent

An informed consent was obtained from each subject. It was obtained using a written consent form administered in English or Igbo depending on the literacy of the subject. Details of the study were carefully explained to the participants before their signatures were obtained. Only those who gave voluntary consent were recruited.

Recruitment, selection, and withdrawal of subjects

Subjects’ recruitment was based on voluntary participation. They were also free to withdraw at any time during the course of the study.

Inclusion criterion

All subjects with confirmed corneal ulceration presenting to the ophthalmic clinic of UNTH within the study period were recruited.

Exclusion criterion

Subjects who did not give their voluntary informed consent were excluded from the study.

Materials

These included a standardized structured questionnaire for collecting relevant information, slit-lamp biomicroscope, Snellen test charts, Snellen illiterate E-chart, Pinhole, Pentorch, single fluorescein strips, glass slides, cover slips, sterile Bard Parker blade (No 15), 4% topical xylocaine and 10% potassium hydroxide, blood agar, chocolate agar, nutrient agar, non-nutrient agar, and Saboraud dextrose agar.

Methods

All recruited participants were managed according to World Health Organization Guidelines for the management of corneal ulcers.[12] A departmental policy was established whereby the researcher was informed of any case of corneal ulcer presenting to the clinic throughout the study period.

Bio-data/history

A standardized structured questionnaire was used for each subject to collect information as regards age, gender, and occupation. The time of onset, laterality, duration of symptoms, and previous eye medications (such as steroids, antibiotics, and traditional eye medications) used before and at the time of presentation was also documented. Any known ocular or systemic disease conditions associated with the patient were also documented.

Clinical examination

The patients’ presenting visual acuities were then measured using the appropriate Snellen optotype for each subject. Subjects with VA less than 6/60 were tested at 3 m with the same optotype. For those with VA less than 3/60, the ability to count fingers at varying distances, perceive hand movement (HM), or perceive light was determined.

Thereafter all patients were examined with a pentorch and slit-lamp biomicroscope to document any signs of trauma to the periocular tissue, lids, and adnexa. The presence of any ocular foreign body on the cornea, conjunctiva, and under the eyelids were sought for. The severities of the corneal ulcers were assessed by determining the presence and extent of any stromal infiltration, height of any present hypopyon, and evidence of anterior chamber reaction. The corneas were then stained with flourescein to highlight the epithelial defect. The location, size (the longest diameter of the ulcers were measured to aid future comparison), depth, and clinical appearance of the corneal ulcers were also documented.

Microbiologic investigations

After ocular examinations of the subjects, two corneal scrapes were obtained under aseptic conditions from the base and periphery (margin) of each ulcer for microbiologic investigations and fungal studies. Corneas at risk of perforation were not scrapped. For these subjects, corneal swabs were however taken for microbiologic investigations.

For all cases, treatment was commenced empirically with broad spectrum topical antibiotics immediately after the clinical assessment and scrapping was carried out. Subsequent treatment was tailored according to the microbiologic diagnosis and sensitivity results.

The posttreatment visual acuities of each subject on discharge from the ward and at 4 weeks of follow up were also documented.

Data analysis

All data were cleaned, edited, and double entered into the computer. Analysis was made using the Statistical Package for Social Sciences (SPSS) software, version 18.0 (SPSS Inc, Chicago, Illinois, USA). Data were subsequently categorized and subjected to descriptive statistical evaluation to yield frequencies, percentages, and proportions. Test for significance between class differences were performed using Chi-squared test (χ2) for categorical variables and Student t test for continuous variables. All P-values <0.05 were considered statistically significant.

Outcome measures

For the purposes of this study, two outcome measures were analyzed to determine the clinical outcome. These included treatment outcome and posttreatment visual outcome. Treatment outcome was categorized into good treatment outcome and poor treatment outcome.

Good treatment outcome included:
  1. Ulcers that healed with minimal or no ocular morbidity


Poor treatment outcome included:
  1. Ulcers that could not heal, leading to perforation and subsequent evisceration
  2. Ulcer that progressed to panophthalmitis and subsequent evisceration
  3. Ulcers that perforated but eventually healed with formation of visually significant adherent leukoma
  4. Ulcer that did not perforate but healed with visually significant corneal opacities
  5. Ulcers that healed but with severe corneal vascularization
  6. Ulcers that developed anterior staphyloma


Posttreatment visual outcome was categorized into:
  1. Visual acuity 6/60 or better (good visual outcome)
  2. Visual acuity worse than 6/60 (poor visual outcome)


6/60 was used as cutoff value for poor visual outcome base on the International Classification of Diseases 11 (2018) which classifies severe distance visual impairment as visual acuity worse than 6/60.[13]


  Results Top


A total of 61 subjects participated in the study comprising 17 (27.9%) females and 44 (72.1%) males with a female to male sex ratio of 1:2.6. The mean age was 46.1 years ± standard deviation of 2.5 with an age range of 6 to 75 years. All 61 subjects had unilateral corneal ulcers. The participants’ demographic characteristics are illustrated in [Figure 2].
Figure 2 Age–sex distribution of 61 participants

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Majority of the participants [22 (36%)] were farmers, 11 (18%) were students, and 8 (13%) were Artisans. Many of the subjects [40 (65.6%)] live in the rural communities surrounding the teaching hospital [Figure 3].
Figure 3 Distribution of the participants by occupation

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Microbiologic profile

Overall, 40 (65.6%) of the corneal scrapings yielded microrganisms. Of the culture positive cases, 21 (52.5%) were purely bacterial, 17 (42.5%) were purely fungal, and 2 (5%) were mixed caused by both bacterial (Staphylococcus aureus) and fungal (Aspergillus fumigatus) organisms in both the cases. There was only one case of presumed viral keratitis. This was presumed upon a dendritic appearance of the ulcer, absence of any microbial isolates despite repeated cultures (viral studies was not carried out due to limited funds), and significant healing of the ulcer upon use of antiviral medication. The commonest bacterial isolate was S. aureus [15 (24.6%)], whereas A. fumigatus [7 (11.5%)] was the commonest fungal isolate. The ulcers caused by fungi ran a more fulminant course.

Systemic diseases

A total of 29 subjects had hypertension. There was no case of diabetes among the subjects.

Contact lens

There was only one case of contact lens use among the participants.

Presenting and posttreatment visual acuity

As shown in [Figure 4], more than half [36 (59.0%)] of the participants presented with a visual acuity worse than 6/60. The best recorded presenting visual acuity of 6/9 was reported in only 3 (4.9%) participants. A presenting visual acuity of HM was recorded in 16 (26.2%) of the participants, whereas 11(18.0%) presented with perception of light. Majority [43 (70.5%)] had a poor posttreatment visual acuity of worse than 6/60. Only 18 (29.5%) had a good posttreatment visual outcome of 6/60 or better.
Figure 4 Presenting visual acuity (VA) and posttreatment visual outcome of the participants

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Treatment outcome/predictors of poor treatment outcome

Of the 61 participants, 35 (57.4%) of the patients had good tratment outcome. The rest [26 (42.6%)] had poor treatment outcome. The poor treatment outcome resulted from complictoins of the cornel ulcers. These included ulcers that could not heal leading to perforation and subsequent evisceration [3 (11.5%)], ulcers that progressed to panopthalmitis with subsequent evisceration [3 (11.5%)], perforated ulcers that healed with visually significant adherent leukoma [5 (19.2%)], visually significant corneal opacities from ulcers that healed without perforation [6 (23.1%)], severe corneal vascularizattion [7 (26.9%)], and anterior staphloma [2 (7.7%)].

Predictors of poor treatment outcome

Predictors of poor treatment outcome included duration of symptoms of more than 1 week before presentation, use of harmful traditional eye medictions (TEMs), size of ulcer ≥4 mm, and presence of hypopyon. Type of microrganism and sex did not have any significant predictive power on poor treatment outcome [Table 1].
Table 1 Predictors of poor treatment outcome

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Predictors of poor posttreatment visual outcome

Of the 18 subjects who had a good posttreatment visual outcome of 6/60 or better, majority [17 (94.4%)] presented within 1 week of noticing their symptoms. Of the 43 subjects who had a poor posttreatment visual outcome worse than 6/60, majority [34 (79.1%)] presented more than 1 week after noticing their symptoms. Shorter duration of symptoms before presentation was associated better visual outcome, whereas longer duration of symptoms was associated with poorer visual outcome (odds ratio = 64.22, P = 0.001). Analysis of the purely bacterial and fungal isolates showed that fungal isolates were significant predictors of poor posttreatment visual outcome. Other factors predictive of poor visual outcome are summarized in [Table 2].
Table 2 Predictors of poor posttreatment visual outcome

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  Discussion Top


Corneal diseases, especially corneal ulceration, are in many regions of developing countries a major cause of significant visual impairment, ocular morbidity, and monocular blindness.[14],[15] Results from our study showed that although majority of the corneal ulcers healed without the need for evisceration, the treatment outcome was nonetheless poor as many of the eyes also had significant complications with the attendant ocular morbidities. Similar findings were also observed in some Nigerian studies.[16],[17] One significant predictor of poor treatment outcome identified in our study was size of ulcer more than 4 mm at presentation. As observed in our survey, several other studies[18],[19],[20],[21] also reported large ulcer size at presentation as significant predictor of poor treatment outcome, although some of these studies[18],[19] were purely on fungal keratitis. The numerous complications observed in our study could also be attributed to late presentation to the clinic by the patients as majority reported to the hospital more than 1 week after noticing their symptoms. This was also shown in the multivariate analysis.

In the same vein, the bivariate analysis showed that duration of symptoms lasting more than 1 week before presentation to the hospital and commencement of standard empirical treatment was a significant predictor of poor visual outcome among the participants (with as many as 70.5% having a posttreatment visual acuity worse than 6/60). Majority 57.4% of the subjects presented to our hospital more than 1 week after noticing their eye symptoms. Similarly, it was observed in some other communities that treatment of corneal disease is often delayed for weeks and patients frequently present to medical facilities with advanced disease including perforated ulcers and completely melted corneas.[12]

In Nigeria and most other developing countries, patients tend to initially seek alternative medical treatment of their eye diseases before accessing orthodox medical care.[22] This accounts for delays in the utilization of orthodox eye-care services and often leads to avoidable blindness especially in blinding eye diseases with time-sensitive course.[22] Several surveys on corneal ulcer patients have indeed shown that similar to the findings in our survey, many present late to hospitals for treatment.[23],[24] These delays have adverse implications as it jeopardizes the treatment and visual outcomes of orthodox eye care and increases the risk of avoidable blindness from ulcerative keratitis. This is a setback to goals of VISION 2020.

Some studies have also shown that the assumption that all persons with eye disease will seek orthodox treatment is unfounded as not all persons requiring treatment present to hospitals.[25],[26] One factor likely to contribute to delays in presenting to hospitals for treatment in the setting of our survey where as many as 36.0% of the subjects were subsistent farmers living in rural areas was cost. This is consistent with reports from other developing countries.[27],[28] Other studies have also established that treatment of corneal ulcers constitutes a significant financial burden on the patient.[8],[29] This therefore brings to light the urgent need to devise appropriate strategies that could help reduce costs of care for corneal ulcers among presenting patients. In addition, effective eye health educational campaigns on the importance of early presentation contrasted with the detrimental effects of late presentation should also be embarked on. The campaigns should be designed to educate the general population on the need for early and prompt presentation following any eye symptoms. It should also be effectively publicized that individuals with abrasions should seek immediate treatment with the appropriate eye health workers. Additionally, attention should be drawn to the fact that any delay could mean blindness. This would help reduce the number of patients who carry their symptoms for long periods before actually presenting to the hospitals with the attendant high risk of poor treatment and visual outcome.

Use of harmful TEMs also had adverse implications on the posttreatment visual acuity in the eyes studied. This was shown in the bivariate analysis where patients who used harmful TEMs were significantly associated with poorer visual outcomes [Table 3]. These findings are similar to the report by Courtright et al.[30] Yorston and Foster[31] in Tanzania also gave similar reports where use of harmful TEMs was associated with hypopyon at presentation and a more central and dense scarring with a subsequent poor visual outcome. Additionally, a significant association has been demonstrated between corneal ulceration, especially peripheral ulceration, and the use of traditional eye medicines in some African communities.[11] Majority of these TEMs contain harmful toxins from microbial organisms and the plant substance itself which can cause devastating damage to the eye. Some of the medications used by the subjects include tangerine juice, human urine, breast milk, sugar solution, and Dettol antiseptic solution. Similar findings on the use of TEMs for self-medication were reported in Nigeria and other countries.[30],[31]
Table 3 Sociodemographics of participants who used traditional eye mediction (TEM), steroids, and contact lens

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To counter these sight-threatening effects, there should be a continuous and well-planned promotive and preventive eye health education programs aimed at educating the public on the devastating effects of harmful TEMs and self-medication. These active community/public eye health interventions and campaigns should be focused more at the grassroots as its use is commoner in these rural communities. On the other hand, the frequent use of harmful TEMs and self-medication suggests inadequacy of or inaccessibility to eye-care services such as primary eye care particularly at the grass root level. Efforts to make these services available to the general population are thus an urgent necessity. This is in consideration of the fact that independent family/community-based medical treatment is rooted in the local medical/cultural practices of the community. Also, because the orthodox health system is often unavailable or unable to provide adequate medical care, harmful TEM use will likely continue especially in the rural communities. Eye-care policy makers and implementers should therefore devise effective strategies such as establishing vision centers manned by trained vision technicians who can screen patients for corneal ulcer and other eye conditions initiate treatment and refer accordingly using WHO treatment and referral guidelines.

In our survey, previous use of topical corticosteroid before presentation was not significantly associated with poor treatment and visual outcomes from the multivariate and bivariate analysis, respectively. This is inconsistent with the study by Wong et al.[32] The disparity may be because many of the steroid preparations used by the participants contained antibiotics such as neomycin as part of the active components. In addition, the dosage, frequency, and duration of use may not have been much or long enough to have caused deleterious effects on the eyes.

On the other hand, the presence of hypoyon was significantly associated with both poor treatment and visual outcome in the subjects. Similar findings were reported by Lalitha et al.[18] and Cameron et al.[33]; however, contrary findings were reported by Sengupta et al.[34] Hypopyon (an indicator of disease severity) usually signifies an outpouring of acute inflammatory cells into the anterior chamber and is associated with increased sloughing of the epithelium and stroma leading to tissue loss and crater formation.[34] Progression of such ulcerative processes can lead to perforation of the cornea. These findings support the need for early intervention so as to limit the extent of visual loss and ocular morbidity. Community-based studies with larger sample size, however, need to be undertaken to corroborate data from this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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