Introduction:

An oncologist advised the treatment of Tab Zetomax 500mg (Angiotensin-converting enzyme inhibitor), Tab Beceptor(Ebastine) 10mg, and tab Myteka 10 mg for seven days.

FOLLOW-UP: (1 week) On examination, visual acuity in the right eye was 6/24, and in the left was 6/6. Near acuity was N14 in the right eye and N6 in the left. Applanation revealed 14mmHg in the right eye and 13 mmHg in the left. Fundus examination through the mydriatic pupil showed markedly regressed edema and hemorrhage. The patient was advised to follow Oncologist.

Follow-up (1 year)

The patient could not follow the visual acuity testing and show to the hospital for a regular eye examination on 12^th/November/2021. The past medical history showed a routine laboratory blood test and bone marrow test every three months with continued medications was tab Glivec (Novartis Imatinib 100 mg). Visual acuity in the right eye was 6/7.5, with best-corrected vision 0.9 with -0.75. Intraocular pressure was 14 mmHg on the right and 13 mmHg on the left. Fundus assessment showed a regressed Roth’s spot with a dull foveal reflex. The optic nerve head was pallor, whereas the peripheral retina was within normal limits. Blood tests results.

Discussion

A Swiss physician Moritz Roth (1849-1914), named Roth spots after Moritz Roth (1849–1914), described it in retinitis septica. 6. These are the retina's impaired coagulation and capillary fragility, which shows a white-centered hemorrhage. Such retinal findings can be the ocular manifestation of many systemic diseases which can also cause serious problems. The retinal white-centered hemorrhage is due to the rupture of capillaries and leakage of blood in intra-retina layers. Histopathophysiological findings such as hemorrhage show platelet-fibrin thrombi, indicating capillary rupture. 7 Thus, disorders that may lead to Roth spots, such as bacterial endocarditis, leukemia, or anemia, cause capillary fragility or intravascular coagulopathy.  The cause of AML is seen as the maturational arrest of cells at the earliest stage of development. The mechanism of the disease is under research, but it is thought to involve the activation and deactivation of genes through translocational chromosomes and other epigenetic disorders.^8,9,10 It results in two processes. Firstly, its cell production has decreased, resulting in different degrees of anemia, neutropenia, and thrombocytopenia. Secondly, the abnormal proliferation of myeloblasts and programmed cell death, known as apoptosis, further accumulates in the blood, bone marrow, liver, and spleen. The differential diagnosis of the ocular Roth spot is seen mainly in bacterial endocarditis. Still, they can also be associated with other systemic diseases such as anemia, leukemia, hypertensive retinopathy, carbon dioxide poisoning, anoxia, preeclampsia, diabetic retinopathy neonatal birth trauma, shaken baby syndrome, connective tissue disorders, vasculitis, or ocular decompression following trabeculectomy^{. 7, 11,12}

Clinical manifestation of leukemia is direct infiltration of leukemic cells, ocular involvement secondary to central nervous system hematological disorders, or drug-related complications. The focus of eye care practitioners is to ask general and specific questions based on the severity of the disease and the ocular manifestation of the disease. The patient must be asked about the history of fatigue or decreased energy levels for the past weeks. Other symptoms include dizziness, dyspnea, chest pain, fever, a history of chest infection, and gum bleeding. Alternatively, history of specific organ infiltration or organ enlargement, gum infiltration, swelling of gum, and altered mental status. Ophthalmologist history taking is based on the duration and severity of vision, pain, redness, or eye deviations.

Visual deterioration associated with Roth spot may be the initial symptom of a severe life-threatening condition with gradual progression. In this case, the patient’s vision was dramatically affected in one eye as the general symptom was not prominent. Such retinal conditions can alert eye care practitioners, ophthalmologists, and Optometrists to tackle medical history. They should be able to refer the patient to oncologists for a careful medical examination.

There were no general severe symptoms. He did not present with other symptoms besides impaired right-eye vision. The sign and symptoms due to bone marrow failure and abnormal production of leukemic cells are variable. As for many patients, especially younger ones, the symptoms prevail from a few days to 1-2 weeks, and others have a more prolonged course that lasts from weeks to months. Anemia, thrombocytopenia, and neutropenia symptoms are also related to bone marrow failure. The significant difference between anemia is the lack of red blood cells, whereas leukemia is cancer-based on various types of cells, such as lymphocytes and myeloid. The most common anemia symptom is fatigue and energy loss for the past weeks. Other symptoms are dizziness, dyspnea, and angina chest pain. Older patient early presents with myocardial infarction in acute cases.

The laboratory investigations required for AML include a complete blood test, biopsy of bone marrow, genetic analysis, and diagnostic investigations. Cytometry is used to assess the immunophenotyping of bone marrow and peripheral blood, and to differentiate AML from acute lymphocytic leukemia. Blood count differentiates thrombocytopenia from anemia. Cytogenetic analysis of the bone marrow provides a guideline about the genetic abnormalities of AML. Coagula show analysis is used to assess the abnormality of disseminated intravascular coagulation(DIC), showing an increased prothrombin time and low fibrinogen level. The subtype of AML, known as acute promyelocytic leukemia, is associated with DIC.  Peripheral blood smear analyzes blast cells.  The blood chemistry profile in AML shows an increased lactate dehydrogenase level (LDH) and raised uric acid. A liver function test and blood urea function are necessary before initiating therapy. Chest radiography gives information about pneumonia and cardiac diseases. Multiple gated acquisition scanning (MUGA) after the diagnosis of AML to regulate cytotoxic caused by chemotherapy. An electrocardiogram should be performed before the commencement of treatment.

As in this case, the blood count of white blood cells is increased despite the reduction of neutrophil cells, and the least absolute neutrophil counts (ANCs) (i.e., < 500 cells/µL, especially < 100 cells/µL) have the highest risk of infection.  Other organ involvement is the history of upper respiratory tract infection and coagulopathy caused by disseminated intravascular coagulation (DIC). The organ infiltration of leukemic cells includes the liver, spleen, gums, and skin. It is commonly seen in monocytic subtypes of AML. As in this patient, splenomegaly is noted in the left upper quadrant as early satiety. Gum bleeding disorder is due to gum infiltration presented to the dentist. Swollen gum, such as Gingivitis, is caused by neutropenia, and thrombocytopenia can cause the gums to bleed. The patients who have WBC counts (>100,000 cells/µL) present with leukocytosis symptoms (i.e., respiratory distress and altered mental status).  It is a medical emergency that requires immediate treatment. Moreover, patients with high leukemic cells present with bone pain due to pressure on the bone marrow. Furthermore, for the investigation, computed tomography (CT) and magnetic resonance imaging should be performed in patients with central nervous system CNS). Suppose a CNS lesion is not detected in CT or MRI. In that case, lumbar puncture is indicated in such patients. ¹³ In case of any sign of cardiac disease and pneumonia chest radiograph is a helpful diagnostic tool. It is vital to evaluate the myocardial infarction once AML is diagnosed because of the cardiotoxic agents used during chemotherapy. For a patient with a history of heart disease, Echocardiography scanning is especially vital to rule out any risk factor for iatrogenic cardiotoxicity (i.e., exposure to cardiotoxic drugs or thoracic radiotherapy^{). [13]}

The treatment of acute myeloid leukemia(AML) is chemotherapy, stem cell transplant, and biological agents. ^{14, 15} It includes general recommendations that account for patients' age, the status of performance, and other refractory disorder or acute promyelocytic leukemia(APL). The patient should be referred for an Oncologist expert decision regarding the treatment guidelines. An oncologist advised the treatment of Tab Zetomax 500mg (Angiotensin-converting enzyme inhibitor), Tab Beceptor(Ebastine) 10mg, and tab Myteka 10 mg for seven days. The standard therapy for AML is chemotherapy with targeted therapeutic drugs. The current chemotherapy drugs used to treat AML are Cytarabine (cytosine arabinoside or ara-C), Cladribine (2-CdA), Fludarabine, and Etoposide (VP-16). It affects normal body cells, causing hair loss, loss of appetite, diarrhea, or constipation, and increases the risk of infection, easy bruising, and fatigue.

Nowadays, the standard of chemotherapy has been lessening for a few patients as a result of all patients undergoing well-designed clinical trials. In the absence of such availability, standard therapy is considered for patients. Readmission is required for a few cases to rule out the toxic effect of chemotherapy. There are specific guidelines for the patients undergoing chemotherapy to refrain from crowded places and people where they can have a contagious disease like viral infections for children. A case with neutropenic fever must promptly be treated with broad-spectrum antibiotics. ^16,17,18

Furthermore, effective transfusion management must be provided for AML patients, illustrated as clotting factors, and transfusion of platelets as guided by patients’ blood tests and bleeding history. The blood products should be irradiated to avoid transfusion-associated graft versus host disease (GVHD).^19,20 In this case, the patient’s leukemic cells were maintained by chemotherapy, and the oncologist was advised to repeat laboratory tests routinely every three months.

For eye practitioners, the essential concern for such patients is detecting the disease at its earliest stage and referring the patient for proper management with an oncologist. The significant decrease in vision due to Roth spots of the retina can create discomfort for the patient if it affects the central vision. Interestingly, in this case, the Roth spots were prevalent in the macular area, a unique presentation of AML. As in many cases, the Roth spots were present in peripheral areas.²¹ Multiple spots scattered across the fundus affected the peripapillary area. They were often numerous and spread out in the whole fundus ^{[22, 23, 24]} or affected the peripapillary region.²¹ These Roth spots can appear and vanish at a great pace, even in an hour; their number and presentation can affect the vision to various degrees. Other retinal conditions, such as pre-retinal hemorrhage, can also be accompanied by Roth spots. ^{25, 21} In my case, the current technological diagnosis was not performed due to its unavailability. Still, the optical coherence tomography findings show hyperreflective deposits and intraretinal pseudocysts, which progress into retinal nerve fiber layer thickening. ²⁶ Such retinal changes have been seen to regress the vision as the underlying reason for the disease is treated. In this case, the patient’s visual acuity was regained after over five months. He showed a drastic improvement in vision during his examination and undergoing treatment for AML. Although many authors have described the condition of Ophthalmological findings, the macular Roth’s spots were less explained. ^{27, 28}

The visual prognosis of AML depends on the diminution of visual acuity affected by Roth’s spot. Ocular signs are more prevalent than symptoms. It rarely happens that a patient may present with a complaint of swelling, anterior uveitis, and infiltration. In his case, visual acuity improved drastically, and Roth’s spots diminished. However, the oncologist regulates a routinely complete blood count after three months.

CONCLUSION

Eye care physicians can diagnose systemic diseases, and the earliest referral of such patients can benefit the patients without getting into adverse effects. AML can also present with ocular findings and other serious associations like exudative retinal detachment. Hence, it is important to know that differential and laboratory investigations must be kept in mind to provide an easy edge diagnosis for managing severe life-threatening diseases.